DEVICE AND METHOD FOR SELECTIVE AND REVERSIBLE MODULATING A STRUCTURE OF THE NERVOUS SYSTEM IN ORDER

专利摘要:
The present invention relates to a system and method for selectively and reversibly modulating targeted nervous or non-nervous tissue of a nervous system for the treatment of pain. Electrical stimulation is delivered to the treatment site which selectively and reversibly modulates the targeted nervous or non-nervous tissue of the nerve structure, inhibiting pain while preserving other motor and motor functions and proprioception.
公开号:FR3092496A1
申请号:FR1912446
申请日:2019-11-06
公开日:2020-08-14
发明作者:Eric A. Schepis；David M. Page；Phillip A. Schorr；Shyamy R. Sastry；Leah Roldan；Natalia Alexeeva；Ryan Caldwell；Amol SOIN
申请人:Avent Inc；
IPC主号:

专利说明:

[0001] CROSS-REFERENCE TO RELATED REQUESTS
[0002] This application claims priority over U.S. Provisional Application No. 62/776,908, filed Friday, December 7, 2018.
[0003] The present invention relates generally to a device and method for modulating the activity of nervous and non-nervous tissues to treat pain. In particular, the invention relates to a device and a method for selectively and reversibly modulating nervous or non-nervous tissue of a nervous structure in order to inhibit pain while preserving other sensory and motor functions, as well as proprioception. .
[0004] BACKGROUND OF THE INVENTION
[0005] Pain can be treated by both destructive and non-destructive methods by disrupting the transmission of pain signals from the body to the brain. Destructive methods are commonly used to treat chronic pain indications and include thermal ablation, cryoablation, chemical ablation (for example, using phenols, lidocaine, Botox ^TM , ultrasound ablation and mechanical transection). However, destruction of nerve structure results in immediate loss of nerve functionality and can lead to long-term atrophy, neuropathy, and ultimately increased pain. Additionally, the mixed nerves and ganglia are generally not targeted by destructive chronic pain interventions due to the desire to maintain motor and painless sensory function. In addition, the destruction of a nerve structure is not conducive to postoperative and perioperative pain management, in which it is desirable to preserve motor and painless sensory function. Therefore, destructive methods of disrupting pain signals are generally not used for acute pain applications such as postoperative pain.
[0006] Non-destructive methods of treating pain include the use of prescription pain medications (e.g. opioids), injections of local anesthetics, topical or injected cocktails that include steroids and other anti-inflammatory agents. inflammation, continuous infusion of local anesthetics, electrical blockade, electrical stimulation, and application of pulsed radiofrequency energy. Each of these methods presents a unique set of challenges that compromise the effectiveness and ease of use of the treatment. For example, prescription pain medications have unwanted side effects and can be addictive. Meanwhile, injections of local anesthetics and cocktails have a short effective duration lasting only a few hours, while continuous infusion of anesthetics requires an external device to be attached to the patient for long-term treatment ( days). In addition, the use of local anesthetics poses a risk of nerve toxicity, vascular toxicity and allergic reactions. Finally, these agents are not selective with respect to the type of nerve activity they block (for example, they block both nerve fiber activity associated with pain and nerve fiber activity associated to motor function).
[0007] Electrical neuromodulation techniques have a lower risk of side effects than chemical interventions and allow for adjustable and local pain management. However, existing electrical blocking technologies are only used to treat chronic post-amputation pain and require the implantation in the patient of an internal pulse generator and nerve sleeve for long-term blocking. As such, the need for surgical implantation imposes a heavy burden on the use of electrical blockade for acute pain applications in small and large nerves, as well as acute pain electrical blockade at head and face. Additionally, even though electrical stimulation devices are commonly used for pain relief, their effectiveness has not been sufficient to date to manage moderate to severe levels of pain, such as that experienced by a migraine patient. severe or chronic, perioperative pain and/or postoperative pain in the days or weeks following an operation. Electrical nerve stimulation devices have also been used in peripheral nerves, on dorsal root ganglia, and in the spinal cord for the treatment of chronic pain. However, they are all burdened with the need for surgical implantation and can undesirably activate painful motor fibers or sensory fibers when applied to mixed nerves or ganglia. In addition, although radiofrequency energy treatment is procedure-based and the patient is not bothered by a take-home device, it cannot be used to treat large nerves and treatment results are inconsistent. for little nerves. Additionally, the selectivity and time to reversibility of radiofrequency energy therapy for acute pain are unknown.
[0008] As such, a need exists for an electrical device and method capable of temporarily and selectively inhibiting pain by modulating neural and non-neural activity in small and large diameter peripheral nerves, cranial nerves, ganglia, autonomic nerves, plexuses, and spinal cord, with effects lasting from days to weeks, when temporary and selective blockade does not pose a risk of neural toxicity, vascular toxicity, or allergy.
[0009] The present invention relates to a system and method for selectively and reversibly modulating targeted nervous or non-nervous tissue of a nervous system for the treatment of pain. Electrical stimulation is delivered to the treatment site that selectively and/or reversibly modulates the targeted nervous or non-nervous tissue of the nerve structure, inhibiting pain while preserving other sensory and motor functions, as well as proprioception. In one aspect, the invention relates to a system for selectively and/or reversibly modulating targeted nervous or non-nervous tissue of a structure of the nervous system (for example, to treat a disease state of a patient). The system includes an electrical stimulation device comprising one or more electrodes (eg, having an appropriate size, shape, and contact area configuration to deliver electrical stimulation to nervous system structure) (eg, unipolar or bipolar) (e.g., a single electrode or an array of electrodes) that delivers electrical stimulation to a treatment site proximate to targeted nervous and non-nervous tissue of the nervous system structure; and a control device configured to connect to one or more electrodes of the electrical stimulation device and to a power source to supply electrical energy to the at least one electrode, the control device being configured to direct operation of the electrical stimulation (eg, controlled by current, voltage, power, and/or temperature) and applying the electrical stimulation to the treatment site through the electrode, and applying electrical stimulation at the treatment site modulating the targeted nerve or non-nerve tissue inhibiting pain and preserving other sensory and motor functions, as well as proprioception.
[0010] In some embodiments, the pain includes at least one of acute pain, postoperative pain, neuropathic pain, chronic pain, and head and face pain.
[0011] In some embodiments, a single application of electrical stimulation at the treatment site selectively modulates the targeted nerve or non-nerve tissue, resulting in subsequent pain inhibition (e.g., for a period of about 1 day to about 30 days, for a period of about 30 days to about 60 days, for a period of about 60 days to about 90 days, for a period of about 90 days to about 120 days, for a period of about 120 days to about 150 days, for a period of about 150 days to about 180 days, for a period of about 180 days to about 270 days, for a period of about 270 days to about 365 days) (for example, when the pain is chronic pain, a single application of electrical stimulation at the treatment site selectively modulates the targeted nerve or non-nerve tissue, resulting in subsequent pain inhibition for a period of approximately 90 days to approximately 365 days).
[0012] In some embodiments, the single application of electrical stimulation at the treatment site selectively modulates the targeted nerve or non-nerve tissue, resulting in the subsequent inhibition of pain for a period of approximately 5 days. at about 30 days.
[0013] In some embodiments, application of the electrical stimulation at the treatment site modulates (eg, selectively modulates and/or reversibly modulates) the targeted nerve or non-nerve tissue inhibiting nerve signal transmission by nerve fibers that are responsible for transmission of pain (e.g., and for transmission of thermoception, autonomic activity, and visceral function), nerve signal transmission through nerve fibers being responsible for other functions sensory and motor, proprioception being preserved, and in the other sensory function being selected from the group consisting of touch, vision, hearing, taste, olfaction and balance.
[0014] In some embodiments, the one or more electrodes are configured (eg, with an appropriate size and shape) to be positioned adjacent to nervous system structure including at least one of a peripheral nerve, a cranial nerve, a ganglion and an autonomic nerve, a plexus and the spinal cord (for example, wherein the ganglion includes at least one of a dorsal root ganglion, sympathetic ganglion, parasympathetic ganglion, sphenopalatine ganglion, gasser's ganglion).
[0015] In some embodiments, the nervous system structure includes a nerve or ganglion (eg, cranial nerve, autonomic nerve, plexus, and spinal cord) having a diameter greater than about 2.5 mm, the or at least one of the electrodes having a size and shape and contact area configuration (eg, an area ranging from 1 mm ² to about 100 mm ² ) sufficient to deliver electrical stimulation to the nerve or ganglion (eg, the controller being configured to generate an appropriate waveform forming the electrical stimulation to modulate (eg, selectively modulate or reversibly modulate) the target nervous or non-nervous tissue of the nervous system structure).
[0016] In some embodiments, application of the electrical stimulation at the treatment site selectively inhibits nerve signal transmission by at least one of a myelinated Aδ fiber and an unmyelinated C fiber disposed in the peripheral nerve while preserving the transmission of the nerve signal by at least one of the Aβ and Aα fibers, and/or the motor fibers.
[0017] In some embodiments, application of the stimulation at the treatment site selectively inhibits nerve signal transmission by at least one of a myelinated Aδ fiber and an unmyelinated C fiber disposed in the peripheral nerve while preserving transmission of the nerve signal by at least one of the Aβ and Aα fibers, and/or the motor fibers of a neighboring nerve or of a neighboring nerve fascicle.
[0018] In some embodiments, the controller is adjustable to vary the electrical stimulation (eg, a parameter of the electrical stimulation) based on measured feedback selected from the group consisting of: measured inhibition of transmission of the nerve signal, a measured temperature (for example at the treatment site, at the electrode(s) or part thereof, on the electrical stimulation device, on the patient's skin) , a contribution from the patient (for example a contribution relating to pain), a feedback corresponding to at least one of the adjustable parameters of the electrical stimulation, a treatment setting associated with a recovery time, an electrode contact impedance, an electrical field generated in the tissue, a patient's physiological response (eg, blood flow, skin conductance, heart rate, muscle activity (eg, electro myography)) and a combination thereof.
[0019] In some embodiments, the controller is configured to vary the duty cycle and/or the wave envelope duration of the electrical stimulation in real time to maximize the voltage delivered to the tissue, without exceeding target tissue temperature at the treatment site (for example, modulating the stimulation duty cycle and/or stimulation envelope to maximize voltage without exceeding a destructive tissue temperature at the treatment site) .
[0020] In some embodiments, the controller is configured to vary the duty cycle and/or the wave envelope duration of the electrical stimulation in real time to maximize the current delivered to the tissue, without exceeding target tissue temperature at the treatment site (eg, modulating the stimulation duty cycle or stimulation envelope to maximize current without exceeding a destructive tissue temperature at the treatment site).
[0021] In some embodiments, the controller is adjustable to vary at least one parameter of the electrical stimulation to modulate (eg, selectively inhibit and/or reversibly inhibit) nerve signal transmission via i) at least one of myelinated Aδ fibers and/or unmyelinated C fibers or ii) a large nerve or large ganglion or large neural structure (e.g., cranial nerve, ganglion, autonomic nerve, plexus, spinal cord, a dorsal root ganglion, a sympathetic ganglion, a parasympathetic ganglion, a sphenopalatine ganglion, a Gasserian ganglion), at least one parameter being selected from the group consisting of a waveform, a wave frequency, wave amplitude, wave envelope duration, electric field strength generated at the electrode (e.g., measured at the electrode or treatment site), wave offset in continuous current u, wave duty cycle, tissue temperature, cooling mechanism parameter (e.g., cooling rate, cooling fluid flow rate, cooling medium pressure, temperature measured at the treatment site or at part of the cooling mechanism) and a treatment duration.
[0022] In some embodiments, the structure of the nervous system includes a peripheral nerve, the controller being adjustable to apply the electrical stimulation to differentially inhibit the function of myelinated Aδ fibers or nerve fibers responsible for sensation sharp/throbbing pain (e.g., Aδ fibers and/or nerve fibers responsible for a sharp/throbbing pain sensation have a higher percentage of inhibited fibers than unmyelinated C fibers or nerve fibers responsible for a feeling of dull/high pain).
[0023] In some embodiments, the structure of the nervous system includes a peripheral nerve, the controller being adjustable to apply the electrical stimulation to differentially inhibit the function of unmyelinated C-fibers or nerve fibers responsible for dull/high-pitched pain sensation (eg, unmyelinated C-fibers and/or nerve fibers responsible for dull/high-pitched pain sensation have a higher percentage of inhibited fibers than myelinated Aδ fibers).
[0024] In some embodiments, the controller is adjustable to vary at least one parameter of the electrical stimulation to modulate (eg, selectively and/or reversibly modulate) nerve signal transmission in a portion of the structure of the nervous system having a cross section less than or equal to the complete section of the structure of the nervous system.
[0025] In some embodiments, the controller is adjustable to vary at least one parameter of the electrical stimulation to reduce an onset response of the nervous system structure and/or an activation of the nervous system structure at the onset of inhibition of the structure of the nervous system.
[0026] In some embodiments, the controller is adjustable to deliver electrical stimulation to the treatment site having a frequency selected from the group consisting of about 100 kHz, about 200 kHz, about 300 kHz, about 400 kHz, about 500 kHz, about 600 kHz, about 700 kHz, about 800 kHz, about 900 kHz and about 1 MHz.
[0027] In some embodiments, the electrical stimulation delivered to the treatment site has an amplitude range between about 5 mA (eg, peak-to-center, corresponding to 10 mA peak-to-peak) to about 1.25 A (peak-to-peak). center, corresponding to 2.5 A peak to peak).
[0028] In some embodiments, the electrical stimulation delivered to the treatment site has an amplitude range between about 10 V and about 500 V (peak-to-center, corresponding to 20-1000 V peak-to-peak).
[0029] In some embodiments, the electrical stimulation delivered to the treatment site has a power range between about 0.1 W and about 1250 W.
[0030] In some embodiments, electrical stimulation delivered to the treatment site generates or induces an electric field strength at the target site and/or an electrode of between about 20 kV/m and about 2000 kV/m.
[0031] In some embodiments, the electrical stimulation delivered to the treatment site has a waveform component (eg, a wave delivered continuously or a wave delivered intermittently (eg, pulsed for a predefined duration)) (for example, as a load balanced wave or as an unbalanced wave), comprising at least one of a sine wave, a square wave, a triangle wave, a pulse wave, a modulated wave form, a frequency modulated wave, an amplitude modulated wave that provides a continuous distribution of electrical stimulation (eg, chirp) at the treatment site, and a combination (eg, additive combination) of these this.
[0032] In some embodiments, the electrical stimulation delivered to the treatment site has a duty cycle of between about 0.1% and about 99%.
[0033] In some embodiments, the electrical stimulation delivered to the treatment site has an interpulse width of between about 1 ms and about 999 ms.
[0034] In some embodiments, electrical stimulation is delivered to the treatment site for up to 30 minutes.
[0035] In some embodiments, the controller is adjustable to apply electrical stimulation while maintaining tissue temperature between about 5°C and about 60°C.
[0036] In some embodiments, the electrical stimulation device includes a device body configured to be implanted into the patient at a location adjacent to the treatment site (eg, placed or implanted percutaneously).
[0037] In some embodiments, the controller includes a pacemaker (eg, function or wave generator) (eg, external function or wave generator), the pacemaker being coupled to both the electrode and at an interface of the controller, operation of the stimulator being directed by the controller to provide electrical stimulation to the electrode.
[0038] In some embodiments, the electrode comprises an electrode assembly in the form of a paddle, sleeve, cylindrical catheter, or thin needle, wire, or probe.
[0039] In some embodiments, the electrode(s) are sized and/or shaped (eg, an electrical contact of the electrode has an area in the range of from about 1 mm ² to about 100 mm ² ) to maximize and to direct the electric field towards the structure of the nervous system.
[0040] In some embodiments, the electrode(s) include at least two electrical contacts (eg, the at least two electrical contacts being configured to be positioned near nervous system structure during treatment) (eg, the controller being configured to operate independently (eg, in a multipole fashion to direct the resultant electric field current) each of the at least two electrical contacts).
[0041] In some embodiments, each of the electrical contacts is located on a single wire, forming a stimulation pair (eg, a cathode and an anode).
[0042] In some embodiments, each of the electrical contacts has a length of between about 1 and 50 mm (e.g., preferably a length of between about 1 mm and about 30 mm, between about 2 mm and about 20 mm, between about 2 mm and about 15 mm, or about 5 mm and 10 mm).
[0043] In some embodiments, the length of each of the electrical contacts is the same.
[0044] In some embodiments, the length of each of the electrical contacts is different.
[0045] In some embodiments, the at least two electrical contacts include a distal electrical contact adjacent a distal end of the electrode and a proximal electrical contact located along the electrode at a location between the distal electrical contact and a distal end. electrode, and a length of the distal electrical contact being greater than a length of the proximal electrical contact (for example, the length of the distal electrical contact may have a length of about 10 mm and the length of the proximal electrical contact may have a length of about 4 mm).
[0046] In some embodiments, the one or more electrodes comprise an electrode assembly in the form of an elongated body, the distal end of the elongated body including a curvature such that a distal end portion of the elongated body extends at an angle relative to a longitudinal axis of the elongated body, the angle of the distal end portion relative to the longitudinal axis of the elongated body being between about 0 and about 50 degrees (eg, preferably between about 5 and about 15 degrees).
[0047] In some embodiments, the distal end portion of the elongated body is straight.
[0048] In some embodiments, the distal end portion of the elongated body is curved.
[0049] In some embodiments, the electrode assembly includes at least two electrical contacts including a distal electrical contact provided on the distal end portion of the elongated body and a proximal electrical contact provided along the elongated body between the distal end and a proximal end of the electrode assembly.
[0050] In some embodiments, the distal electrical contact is sized and configured to interface with targeted neural or non-nervous tissue of the nervous system structure, and the proximal electrical contact is sized and configured to be positioned within underlying tissue. cutaneous (e.g. fat, fascia, muscle).
[0051] In certain embodiments, each of the electrode(s) comprises at least two electrical contacts, each of the electrical contacts being located on the same side of the elongated body of the electrode.
[0052] In some embodiments, the conductive regions of each of the electrical contacts are on the same side of the elongated body and do not deliver electrical energy circumferentially to a portion of a circumference of the elongated body without electrical contacts (e.g., the electrical contact does not deliver electrical energy circumferentially to a short axis of the wire, thereby providing voltage field shaping and current direction).
[0053] In some embodiments, the system further includes a resistor electrically positioned in series with an electrical contact included in the electrode(s).
[0054] In some embodiments, the electrical contacts provided on the electrode(s) are formed from a higher impedance or high capacitance material.
[0055] In some embodiments, the electrical contacts provided on the electrode(s) have a smooth curvilinear shaped perimeter.
[0056] In some embodiments, the electrical contacts provided on the electrode(s) have an oval-shaped perimeter.
[0057] In certain embodiments, the electrical contacts provided on the electrode(s) have a rectilinear shaped perimeter.
[0058] In some embodiments, the system further includes a temperature measuring device (eg, thermocouple, thermistor) provided on the electrode(s) to provide a measurement of tissue temperature.
[0059] In some embodiments, at least one of an electrical contact and a temperature sensing device provided on the electrode(s) is printed from an electrically and thermally conductive material.
[0060] In some embodiments, the electrical contacts provided on the electrode(s) extend partially around a circumference of the corresponding electrode, an arc length of the electrical contact being less than 180 degrees, such that the electrical contact extends around less than half the circumference of the electrode.
[0061] In some embodiments, the electrode is electrically coupled to the controller via a circumferentially shaped contact surface provided on the electrode and a corresponding circumferentially shaped contact surface provided on a wire electrically coupled to the controller.
[0062] In some embodiments, the circumferentially shaped contact surface includes more than one circumferentially shaped contact surface arranged concentrically around the longitudinal axis of the electrode (e.g., four circumferentially shaped contact surfaces of variable diameter), a wire electrically coupled between the electrode and the generator comprising more than one contact surface of corresponding circumferential shape arranged concentrically around a longitudinal axis of the wire (for example, four contact surfaces of variable diameter circumferential in shape).
[0063] In some embodiments, the contact surfaces of the circumferentially shaped electrode are separated by a dielectric layer (eg, electrically insulating materials and/or air supplied between adjacent conductive surfaces), the contact surfaces circumferentially shaped wire being separated by dielectric layer (eg, electrically insulating materials and/or air provided between adjacent conductive surfaces).
[0064] In some embodiments, the electrical circuit of the electrodes extends inside the electrode inside the circumferentially shaped contact surface.
[0065] In some embodiments, at least one of the electrode(s) is a unipolar electrode configured to be positioned on a contact surface of the stimulation device, and a return electrode is positioned on an exterior surface of the patient's skin.
[0066] In some embodiments, the stimulation device is reusable.
[0067] In some embodiments, the stimulation device is disposable.
[0068] In some embodiments, the system further includes a user interface (including, for example, a display (eg, to provide an indication of the status of the controller, pacing device, patient)), the with the user interface configured to receive input from the user, directing the application of the electrical stimulation to the treatment site (eg, to vary pain inhibition (while preserving other sensory and motor function and proprioception).
[0069] In some embodiments, the system further includes a display coupled to at least one of the controller and the stimulation device, the display providing an indication of the status of the stimulation device.
[0070] In some embodiments, the system further includes a temperature sensor (eg, thermistor, thermocouple) coupled to the stimulation device to measure a temperature of at least one of i) a contact surface of the stimulation device and ii) patient tissue adjacent to the contact surface or electrode, the temperature sensor being coupled to the controller and providing thermal feedback regarding a measured temperature, the controller being adjustable to vary at least one parameter of electrical stimulation (eg, by the controller or by the user) in response to thermal feedback received from the temperature sensor (eg, to adjust contact surface temperature and maintain the temperature of the patient's tissue below a tissue destructive temperature and/or to maintain the temperature of the contact surface of the stimulation device below the tissue destructive temperature).
[0071] In some embodiments, the system further includes a cooling mechanism configured to provide a cooling effect at the treatment site (eg, the contact surface of the stimulation device), the cooling effect preventing damage (eg, by pre-cooling or maintaining temperature when electrical stimulation is delivered) at the treatment site (eg, by keeping patient tissue temperatures below a tissue-killing temperature) .
[0072] In another aspect, the invention relates to a method for selectively and reversibly modulating targeted nervous and non-nervous tissue of a nervous system structure with the application of electrical stimulation (e.g., single application of stimulation electric) in order to treat a medical condition of a patient. The method includes identifying a targeted nervous system structure; positioning an electrical stimulation device at a treatment site proximate to the targeted nervous and non-nervous tissue of the nervous system structure, the electrical stimulation device comprising an electrode that provides electrical stimulation at the site of processing ; delivering electrical stimulation to the treatment site via the electrode; the application of electrical stimulation at the treatment site selectively modulating the targeted nervous or non-nervous tissue of the nervous system structure inhibiting pain and preserving other sensory and motor function, as well as proprioception; and applying the electrical stimulation at the treatment site selectively modulating the targeted nerve or non-nerve tissue and subsequently inhibiting pain (e.g., for a period of about 1 day to about 30 days, for a period from about 30 days to about 60 days, for a period of about 60 days to about 90 days, for a period of about 90 days to about 120 days, for a period of about 120 days to about 150 days, for a period of about 150 days to about 180 days, for a period of about 180 days to about 270 days, for a period of about 270 days to about 365 days).
[0073] In some embodiments, the nervous system structure includes at least one peripheral nerve, cranial nerve, ganglion (e.g., the ganglion including at least one of a dorsal root ganglion, sympathetic ganglion, parasympathetic ganglion, a sphenopalatine ganglion, a gasser's ganglion, a plexus, the spinal cord), an autonomic nerve and an autonomic ganglion.
[0074] In some embodiments, the application of electrical stimulation at the treatment site selectively modulates targeted nerve or non-nerve tissue inhibiting nerve signal transmission through nerve fibers responsible for pain transmission, transmission nerve signal through nerve fibers responsible for the other sensory and motor functions, and proprioception being preserved, and the other sensory function includes at least one of touch, vision, hearing, taste, olfaction and balance.
[0075] In some embodiments, the pain includes at least one of acute pain, operative pain, post-operative pain, traumatic pain, neuropathic pain, chronic pain, and head and face pain.
[0076] In some embodiments, when the pain is acute pain, the electrical stimulation is applied at least immediately before a surgical procedure, intraoperatively, and immediately after a surgical procedure or trauma.
[0077] In some embodiments, the electrical stimulation is delivered to the treatment site more than 24 hours prior to a surgical procedure.
[0078] In some embodiments, when the pain is postoperative pain following a knee replacement procedure, electrical stimulation is applied to the femoral nerve, sciatic nerve, obturator nerve, and lateral cutaneous nerve and nerve branches, or a combination thereof.
[0079] In some embodiments, when the pain is shoulder pain, electrical stimulation is applied to the brachial plexus, axillary nerve, suprascapular nerve, and lateral pectoral nerve, or a combination thereof.
[0080] In some embodiments, when the pain is associated with a medical procedure and/or trauma to the arm and/or hand, the electrical stimulation is applied individually to the medial, ulnar, and radial nerves or to the brachial plexus, or a combination thereof.
[0081] In some embodiments, when the pain is associated with a medical procedure and/or trauma to the ankle and/or foot, electrical stimulation is applied to the tibial, peroneal/sural, and saphenous nerves, or a combination of these.
[0082] In some embodiments, when pain is associated with hip replacement surgery, electrical stimulation is applied to the femoral, sciatic, or obturator nerves (e.g., common obturator nerve before its branching into anterior and posterior nerves) and/or to a plexus, or a combination thereof.
[0083] In some embodiments, when the pain is associated with anterior cruciate ligament (ACL) repair, electrical stimulation is applied to the femoral or sciatic nerve, or a combination thereof.
[0084] In some embodiments, the pain is neuropathic pain or chronic pain, the electrical stimulation is used to provide a bolus of therapeutic treatment on demand.
[0085] In some embodiments, the step of positioning the electrical stimulation device proximate the treatment site includes: positioning the electrode proximate nervous system structure percutaneously through an opening in the patient's skin ; or implant the electrode in the patient at a location adjacent to the treatment site.
[0086] In some embodiments, the step of positioning the electrical stimulation device proximate the treatment site further includes: delivering an initial electrical stimulation to the treatment site via the electrode; measuring at least one of a voltage and a current on the electrode; and adjusting a position of the electrode at the treatment site until the measured voltage and current correspond to a threshold voltage and a threshold current, respectively.
[0087] In some embodiments, the method further comprises adjusting at least one parameter of the electrical stimulation to selectively inhibit transmission of the nerve signal through the targeted nerve or non-nerve tissue, said at least one parameter being selected in the group consisting of waveform, wave frequency, wave amplitude, wave envelope duration, electric field strength generated at the electrode (e.g., measured at the electrode or treatment site), DC wave offset, wave duty cycle, tissue temperature, cooling mechanism parameter (e.g., cooling rate, flow rate of the cooling fluid, a pressure of the cooling medium, a temperature measured at the level of the treatment site or at the level of a part of the cooling mechanism) and a duration of treatment.
[0088] In some embodiments, the method further includes modulating the duty cycle or wave envelope duration of the real-time electrical stimulation to maximize the voltage delivered to the treatment site without exceeding a temperature of the target tissue at the treatment site (for example, modulation of the stimulation duty cycle or stimulation envelope to maximize voltage without exceeding a destructive tissue temperature at the treatment site).
[0089] In some embodiments, the method further includes modulating the duty cycle or wave envelope duration of the real - time electrical stimulation to maximize the current delivered to the treatment site without exceeding a tissue temperature target at the treatment site (eg, modulation of stimulation duty cycle or stimulation envelope to maximize current without exceeding irreversibly tissue-destructive temperature).
[0090] In some embodiments, the method further includes gradually increasing the stimulation amplitude of the electrical stimulation to a plateau in amplitude.
[0091] In some embodiments, the method further includes adjusting the controller to vary the electrical stimulation based on measured feedback selected from the group consisting of: measured inhibition of nerve signal transmission, the measured temperature (e.g. at the treatment site, at the electrode(s) or part thereof, on the electrical stimulation device, on the patient's skin), a contribution from the patient (for example a contribution concerning the pain), a feedback corresponding to at least one of the adjustable parameters, a treatment setting associated with a recovery time, an electrode contact impedance, an electric field generated in the tissue, a patient's physiological response (eg, blood flow, skin conductance, heart rate, muscle activity (eg, electromyography)) and a combination thereof.
[0092] In some embodiments, the electrode includes a first and a second electrode that operate independently, the delivery of electrical stimulation to the treatment site via the electrode further comprising delivering a first electrical stimulation via the first electrode and the delivery of a second electrical stimulation via the second electrode, wherein the first and second electrical stimulations are emitted intermittently, wherein the first electrical stimulation is alternated with respect to the second electrical stimulation such that a an on cycle of the first electrical stimulation occurs during an off cycle of the second electrical stimulation and an on cycle of the second electrical stimulation occurs during an off cycle of the first electrical stimulation.
[0093] In certain embodiments, the method further comprises measuring, at the level of a temperature sensor (for example, a thermistor, a thermocouple), a temperature of at least one element among a contact surface of the device device and patient tissue adjacent to the contact surface during delivery of the electrical stimulation, the temperature sensor providing thermal feedback regarding a measured temperature to the stimulation device; and adjusting the electrical stimulation (eg, adjusting a parameter of the electrical stimulation) in response to thermal feedback received from the temperature sensor to create a cooling effect on at least one of the surface of the stimulation device and the patient tissue adjacent to the contact surface.
[0094] In certain embodiments, the method further comprises measuring, at the level of a temperature sensor (for example, a thermistor, a thermocouple), a temperature of at least one element among a contact surface of the device device and patient tissue adjacent to the contact surface during delivery of the electrical stimulation, the temperature sensor providing thermal feedback regarding the measured temperature to the stimulation device; activating a cooling mechanism to cool the contact surface of the stimulation device in response to thermal feedback received from the temperature sensor, the cooling of the contact surface avoiding damage to patient tissue when stimulation electrical energy is delivered by maintaining patient tissue temperatures below a tissue destructive temperature, and activating a cooling mechanism to maintain the temperature of the contact surface of the stimulation device below the destructive temperature tissue in response to thermal feedback regarding the measured temperature received from the temperature sensor.
[0095] In another aspect, the invention relates to a non-transitory computer-readable medium. The computer-readable medium having instructions stored thereon, in which execution of the instructions by a processor causes the processor to perform any of the processes listed above.
[0096] Details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects and advantages of the invention will be apparent from the description and the drawings, as well as from the claims.
[0097] The patent or application file contains at least one color drawing. Copies of this patent or patent application publication with color drawings will be furnished by the Office upon request and against payment of the necessary fee.
[0098] Figure 1 is a schematic representation of an example electrical stimulation device.
[0099] Figure 2A is a schematic representation of the electrical stimulation device of Figure 1.
[0100] Figure 2B is a schematic representation of the electrical stimulation device of Figure 1.
[0101] Figures 3A-3G are schematic representations of exemplary percutaneous electrodes.
[0102] Figure 4A is a schematic representation of an example of a percutaneous electrode positioned adjacent to a target nerve.
[0103] Figure 4B is a schematic cross-sectional view of the example electrode of Figure 4A.
[0104] Figure 5 shows various examples of bipolar electrical contact and electrode configurations.
[0105] Figures 6A and 6B are an example of an electrode connection.
[0106] Figure 7A is an example of electrical stimulation, and corresponding control parameters, that can be applied to nervous tissue and/or nearby tissues to selectively and/or reversibly inhibit nervous system activities.
[0107] Figures 7B, 7C, 7D, 7E, 7F, 7G, 7H, 7I, 7J, 7K, 7L, 7M, 7N, 7O, and 7P each show a waveform for electrical stimulation.
[0108] Figure 8 is a schematic representation of percutaneous electrode placement and delivery of electrical stimulation to a target nerve structure.
[0109] Figures 9A and 9B are schematic representations of electrode placement and delivery of electrical stimulation to the sphenopalatine ganglion.
[0110] Figure 10 is a table showing the experimental results.
[0111] Figure 11 is a table showing the experimental results.
[0112] Like reference symbols in different drawings indicate like elements.
[0113] DEFINITIONS
[0114] The following description of certain examples of the inventive concepts should not be used to limit the scope of the claims. Other examples, features, aspects, embodiments and advantages will become apparent to those skilled in the art from the following description. As will be understood, the device and/or methods are capable of including other obvious and different aspects, all without departing from the spirit of the inventive concepts. Accordingly, the drawings and description should be considered illustrative and not restrictive.
[0115] For the purposes of this description, certain aspects, advantages and new features of the embodiments of the present description are described here. The methods, systems and apparatus described should not be considered limiting in any way. Instead, this description is directed to all new and non-obvious features and aspects of the various described embodiments, alone and in various combinations and sub-combinations with each other. The described methods, systems, and apparatuses are not limited to any specific aspect, any specific feature, or combination thereof, nor do the described methods, systems, and apparatuses require that any one or more specific benefits are present or problems are solved.
[0116] Functions, integers, characteristics, compounds, chemical moieties, or groups described in conjunction with a particular aspect, embodiment, or example of the invention should be understood to apply to any other aspect , embodiment, or example described herein, unless inconsistent therewith. All of the features disclosed in this description (including the claims, abstract and accompanying drawings) and/or all of the steps of any process or method so disclosed may be combined in any combination, except for combinations where at least some of these features and/or steps are mutually exclusive. The invention is not limited to the details of the previous embodiments. The invention applies to any new feature or new combination of features described in this description (including the claims, the abstract and the accompanying drawings), to any new step or new combination, d steps of any process or method so disclosed.
[0117] Ranges may be expressed herein as "about" one particular value and/or to "about" another particular value. When such a range is expressed, another aspect includes from a particular value and/or to another particular value. Similarly, when values are expressed as approximations, using the antecedent "about", it will be understood that the particular value forms another aspect. It will further be understood that the endpoints of each of the ranges are significant both with respect to the other endpoint and independently of the other endpoint.
[0118] The terms "possible" and "possibly" as used herein mean that the event or circumstance described below may or may not occur and that the description includes instances where such event or circumstance occurs and instances where it does not. product not.
[0119] The terms "proximal" and "distal" are used herein as relative terms which refer to regions of a nerve, positions of nerves or regions of a stimulation device. "Proximal" means a position closer to the spinal cord, brain, or central nervous system, while "distal" indicates a position farther from the spinal cord, brain, or central nervous system. When referring to position on a neural structure in the peripheral nervous system or along an appendage, proximal and distal refer to positions either closer to the central nervous system or farther from the central nervous system along the pathway followed by that neural structure or appendage. When referring to position on a neural structure in the spinal cord, proximal and distal refer to positions either closer to the brain or farther from the brain along the path followed by the neural structure.
[0120] Throughout the description and claims of the invention, the word "include" and variations of the word, such as "comprising" and "includes", mean "including, but not limited to" and are not intended to exclude, for example, other additives, components, integers or steps. The terms "example" and "for example" mean "an example of" and are not intended to give an indication of a preferred or ideal aspect. The term "as" is not used in a restrictive sense, but for explanatory purposes.
[0121] As used herein, the term "nerve structure" or "neural structure" refers to a structure comprising nervous and non-nerve tissue. In addition to nerve tissue (such as neurons and components of neurons, including axons, cell bodies, dendrites, and synapses of neurons), nerve structures can also include non-nerve tissue such as cells glial cells, Schwann cells, myelin, immune cells, connective tissue, epithelial cells, neuroglial cells, astrocytes, microglial cells, ependymal cells, oligodendrocytes, satellite cells, cardiovascular cells, cells blood, etc.
[0122] The term "stimulation electrode" herein, also referred to as "cathode" in the case of unipolar stimulation, refers to an electrode responsible for delivering therapeutic energy to the nerve. In the case of bipolar or multipolar stimulation, all electrical contacts are considered stimulation electrodes.
[0123] The term "return electrode" herein, also referred to as an "anode" in the case of unipolar stimulation, refers to an electrode responsible for providing a return path for current flowing through the body. For example, the return electrode provides a return path for current that is delivered to the target neural structure via the stimulation electrode.
[0124] In this document, the terms "electrical signal", "electrical stimulation", "electrical stimulation signal" and "stimulation wave" refer to the electrical signal delivered by the control device to the tissue by means of the stimulation electrodes or, in the case of unipolar stimulation, by means of the stimulation electrode and the return electrode. For example, the electrical signal can be described as a time-varying voltage, current, power, or other electrical measurement. The delivery of the electrical signal to the target tissue is called electrical treatment, electrical therapy or simply treatment or therapy. The electric signal creates an electric field in the tissue, so the control of the electric signal strongly influences the control of the electric field in the tissue.
[0125] The term "processing site" herein refers to the site of the neural and non-neural structure to which the electrical signal is delivered by means of the electrode or electrodes.
[0126] In the present, the term "modulate" means a modification or a change in the transmission of information. For example, it includes both excitation, stimulation, and inhibition/stopping of the passage of impulses along the axon of the neuron in a nerve. Modulation of nerve fiber activity includes inhibition of nerve signal transmission to the point of creating a blocking effect, including a partial or complete blocking effect. Modulating nerve activity also includes altering the traffic of molecules such as macromolecules along the nerve fiber. Modulation of nerve activity also includes changing function downstream of the neuron (e.g. at cell bodies and synapses), altering signaling in ways that alter signaling in other neurons (e.g. central nervous system neurons such as the spinal cord or brain), altering the function of non-nervous tissue within the neural structure, or otherwise altering processes, function, or activity within target nerve or non-nerve tissue.
[0127] As used herein, the terms "inhibit" and "attenuate" refer to any rate of reduction, including partial or complete reduction of nerve signal activity through a nerve structure, e.g., reduction in the passage of impulses along the axon of the neuron in a nerve.
[0128] As used herein, the term "percutaneous" means applied electrical stimulation using one or more electrodes penetrating through the surface of the skin so that an electrode delivering electrical stimulation to a target nerve located under the skin is also located under the skin. . For percutaneous electrical stimulation, it is contemplated that return electrodes or anodes may be located under the skin or on the surface of the skin. The term "percutaneous electrode" refers to sets of electrodes inserted through the skin and directed into the vicinity of the nerve (mm to cm distance) in a minimally invasive manner to electrically affect the physiology of the neural structure.
[0129] Herein, the terms "pain sensation" and "painful sensation" refer to an unpleasant sensation generated, for example, by the activation of sensory nociceptors. Nociception describes the perception of acute pain and is usually caused by the activation of sensory nociceptors or by the disruption of nociceptor pathways (eg, severed neurons or disrupted nociceptors). The sensation of chronic pain can also be generated by the activation of nerve fibres, which leads to an unpleasant perception similar in nature to that generated by the activation of nociceptors (for example, neuropathic pain). In some cases, for example after surgery to treat chronic pain, acute pain sensation and chronic pain sensation may contribute in a mixed way to the overall pain sensation.
[0130] Herein, the term "target nerve" is synonymous with "neural structure" or "nerve structure" and refers, for example, to mixed nerves containing motor nerve fibers and sensory nerve fibers. They can also be sensory nerves containing only sensory nerve fibers and/or motor nerves containing only motor nerve fibers.
[0131] The term "transmucosal" herein refers to electrical stimulation applied to mucosal tissue overlying a targeted nerve structure using one or more electrodes. The electrical stimulation travels through the mucosal tissue to the targeted nerve structure.
[0132] The terms "preserve" and "preservation" herein refer to cases in which nerve function is partially but not completely maintained, as well as cases in which function is completely maintained. In comparative cases, one function may be inhibited while another is preserved, suggesting that, in a comparative fashion, the inhibited function suffered a greater reduction than that suffered by the preserved function. Specifically, in comparative cases, inhibition of one function and preservation of another function does not require complete preservation or complete inhibition of either function.
[0133] DETAILED DESCRIPTION
[0134] ANATOMY AND PHYSIOLOGY
[0135] As described above and as will be explained in more detail below, the present invention relates to a device and a method for selectively and reversibly modulating the targeted nervous or non-nervous tissue of a nervous structure by the application an electrical signal to inhibit pain while preserving other sensory and motor functions, as well as proprioception. The device and method can be used to treat acute pain (such as operative pain, post-operative pain, painful trauma), neuropathic pain, chronic pain, and head and face pain (such as migraine, cluster headache, occipital neuralgia, tension headache, sinus headache, cervicogenic headache, postherpetic neuralgia, posttraumatic pain, chronic daily headache (transformed migraine) via the application of an electrical signal to target nerve or non-nerve tissue of a nerve structure to modulate or inhibit nerve signaling.
[0136] Pain is a harmful perception generated in the conscious. In healthy humans, the perception of pain is generated by the activation of sensory nociceptors and the subsequent transmission of nociceptive signals to the brain through one or more neural pathways. Pain can be created by the activation of a neural pathway, at any point in that neural pathway, resulting in the perception of pain. In healthy humans, pain-generating neural pathways are typically activated via sensory nociceptors, which are sensory nerve endings tuned to detect and signal harmful events (e.g. harmful mechanical or thermal tissue damage). This type of pain usually represents a real harmful pathology and this type of pain disappears when the harmful pathology is resolved. In cases where the harmful event is not chronic tissue dysfunction, this type of pain is called acute pain. In contrast, chronic pain represents pathologies in which pain-generating neural pathways are persistently modulated due to chronic tissue dysfunction or nerve dysfunction. This may be due to actual activation of sensory nociceptors at a site of chronically dysfunctional tissue or to dysfunction of nerve tissue or tissue supporting nerve tissue that results in modulation at any point in pain-producing neural pathways.
[0137] Interventions aimed at treating pain can be designed to directly or indirectly modulate nerve signal transmission through pain-generating neural pathways at any level of those pathways. For example, direct blockade of axonal conduction in nerve fibers attached to sensory nociceptors can block pain perception. As a further example, indirect modulation of synaptic transmission in the spinal cord or nerve ganglia can be achieved by activating or blocking other inputs into the spinal cord or ganglia and can result in modulation along a pain-producing neural pathway. As another example, inhibition of parasympathetic outflow in the sphenopalatine ganglion may indirectly influence head and facial pain, such as migraine, by modulating sensory inputs to the brain (e.g. via the superior salivatory nucleus) . Thus, it is desirable to target various neural structures when modulating and treating acute and chronic pain.
[0138] Nerve structures targeted include peripheral nerves (small diameter and large diameter), cranial nerves, ganglia, autonomic nerves, plexuses and spinal cord. Ganglia include at least one of dorsal root ganglia, sympathetic ganglia, parasympathetic ganglia, sphenopalatine ganglion, gasser ganglia, and autonomic ganglia in general. Generally, the large peripheral nerves are the peripheral nerves having a diameter greater than about 2.5 mm. Major peripheral nerves include, for example, femoral nerve, sciatic nerve, vagus nerve, tibial nerve, peroneal nerve, median nerve, radial nerve, and ulnar nerve. Small peripheral nerves include, for example, the saphenous nerve, the sural nerve, the genicular nerves, the cranial nerves (such as the trigeminal nerve and the occipital nerve), the obturator nerve and the distal parts of the larger nerves (such as the distal parts of the vagus, peroneal, median, radial and ulnar nerves). Targeted ganglia may include dorsal root ganglia, sympathetic ganglia, parasympathetic ganglia, sphenopalatine ganglion (SPG), gasser's ganglia, plexus, and spinal cord. Each of these nerve structures includes nerve tissue as well as non-nerve tissue that supports nerve tissue and can influence the transmission of information along pain-producing neural pathways. Example of non-nervous tissue may include, for example, glial cells, Schwann cells, myelin, immune cells, connective tissue, epithelial cells, neuroglial cells, astrocytes, microglial cells, ependymal cells , oligodendrocytes, satellite cells, cardiovascular cells, blood cells, etc. By nerve tissue is generally meant neurons comprising components such as axons, cell bodies, dendrites, receptor terminals, receptors and synapses.
[0139] Importantly, in the context of the present invention, modulation of nerve tissue (neurons including components such as axons, cell bodies, dendrites, receptor terminals, receptors and synapses) and/or tissue non-nervous (such as glial cells, Schwann cells, myelin, immune cells, connective tissue, epithelial cells, neuroglial cells, astrocytes, microglial cells, ependymal cells, oligodendrocytes, satellite cells , cardiovascular cells, blood cells, etc.) may be responsible in part or in whole for the therapeutic inhibition of pain.
[0140] Peripheral nerves are mainly composed of axons, while other neural structures, such as ganglia and spinal cord, consist of many components including axons, cell bodies, dendrites, and synapses. Within a nerve structure, there is variability in the nature of these components, including variability in size, shape, and interface with non-nerve supporting tissue. For example, peripheral nerves often contain large and small diameter axons. Schwann cells are non-nerve support cells that surround certain axons and comprise an insulating envelope rich in layers of lipid bilayers called myelin sheath. Some axons are surrounded by a myelin sheath, and some axons are not surrounded by a myelin sheath. Generally, the structure of the different nerve components is related to their function. For example, large-diameter axons generally transmit nerve signals faster than small-diameter axons due to the relatively large increase in axial conductance compared to a modest increase in membrane conductance with diameter. Similarly, the presence of a myelin sheath on large diameter axons further increases the conduction velocity of the action potential by increasing the resistance to transmembrane current flow between unmyelinated areas of the axon, called nodes of Ranvier. Ranvier's nodes are short unmyelinated parts of fibers. Action potentials are relayed down the axon by a burst of transmembrane current flow at each subsequent node of Ranvier. Peripheral nerve axons that typically convey information from the periphery to the central nervous system (e.g. sensory information, including pain) are often referred to as afferent fibers, while axons that typically convey information from the central nervous system to the periphery (eg motor information) are often called efferent fibers.
[0141] The term "A-fiber" herein refers to peripheral afferent or efferent myelinated axons of the somatic nervous system. Broadly speaking, A-fibers are associated with proprioception, somatic motor skills, sensations of touch and pressure, as well as sensations of pain and temperature. A-fibers typically have a diameter of about 1 to 22 micrometers (μm) and conduction velocities between about 2 meters per second (m/s) and over 100 m/s. Each A-fiber has dedicated Schwann cells forming the myelin sheath around the fiber. As described above, the myelin sheath has a high lipid content, increasing electrical resistance to transmembrane current flow and contributing to the high conduction velocity of action potentials along the nerve fiber. A fibers include alpha, beta, delta, and gamma fibers. Alpha, beta, and gamma A-fibers have diameters between 5 and 20 micrometers (μm) and are associated with motor function, low-threshold sensory function, and proprioception, but not pain. A-delta fibers are associated with pain and have smaller diameters in the range of 1 micrometer to 5 micrometers (μm).
[0142] The term "C-fiber" herein refers to unmyelinated peripheral axons of the somatic nervous system having conduction velocities less than about 2 m/s. C-fibers are about 0.2 to 1.5 micrometers (μm) in diameter and include dorsal root and sympathetic fibers. They are mainly associated with sensations such as pain and temperature, some mechanoreception, reflex reactions, autonomic effector activity and visceral function.
[0143] In a peripheral nerve, the sensation of pain perceived as dull and persistent is often referred to as “slow pain” and is transmitted in the peripheral nerves by C-fibers which transmit nerve signals relatively slowly. The sensation of pain perceived as sharp and rapid is often referred to as “rapid pain” and is transmitted in peripheral nerves by Aδ fibers having a higher conduction velocity than C fibers. Aδ fibers generally include sensory axons of small diameter lightly myelinated compared to unmyelinated C-fibers. Acute and chronic pain can involve the Aδ and C fibers.
[0144] In addition to the examples given above for axons of peripheral nerves, similar principles of structure and function for components of neuronal structures, such as axons, cell bodies, dendrites, receptor terminals, receptors and synapses apply to different neural structures including peripheral nerve, cranial nerve, ganglion and autonomic nerve, plexus and spinal cord. Subcellular structures within components of non-nervous and nervous tissues, such as cell membranes, lipid bilayers, ion channels, mitochondria, microtubules, nucleus, vacuoles, and other cytoplasm components are also related to the functioning of these components of neural structures. Additionally, downstream structures (e.g., cellular and subcellular structures downstream of the processing site) may also be functionally or structurally impacted primarily or secondary by nerve treatments (e.g., downstream modulation of transcription gene, synaptic transmission, epigenetics or modulation along multiple molecular signaling cascades in a neuron). The downstream molecular and cellular machinery, and even the connectivity and communication between cells, can be very different for pain pathways compared to motor, nonpain sensory, and proprioceptive pathways.
[0145] As an additional example, the sphenopalatine ganglion is made up of parasympathetic neurons, sympathetic neurons, and sensory neurons. In the sympathetic ganglion, cell bodies and synapses are present for parasympathetic neurons, but not for sympathetic or sensory neurons. On the contrary, only the axons of sympathetic and sensory neurons cross the sphenopalatine ganglion. The device and method of the present invention can be used to selectively and/or reversibly modulate nerve signal transmission in any of the types of neural structure (e.g., cell bodies, synapses, axons) without modulate the other neural structures present in the ganglion. For example, modulation or inhibition of transmission via the parasympathetic neuronal pathway, such as by inhibiting signal transmission via cell bodies or synapses in the sphenopalatine ganglion, can be achieved while preserving signaling via sympathetic pathways and at least some of the sensory pathways. As a further example, modulation or inhibition of transmission via small-diameter sensory neurons can be achieved while preserving signaling via sympathetic, parasympathetic, and other sensory fiber pathways. As a further example, modulation of the parasympathetic pathway and the small-diameter sensory pathway can be achieved while preserving signaling via all other ganglion pathways. Notably, each type of nerve component in a neural structure may have its own non-nerve supporting tissue, which contributes to the ability to selectively target modulation through specific pathways.
[0146] As will be described in more detail below, the device and method of the present invention can be used to selectively and reversibly modulate nerve signal transmission, for example by inhibiting or blocking nerve signal transmission, so as to to inhibit pain. This selective and reversible pain inhibition does not present a risk of neuronal toxicity, vascular toxicity or injectable chemical allergy. The device of the present invention is non-destructive to the target nerve structure and is suitable for the treatment of chronic pain indications without risks of atrophy, neuropathy and pain, and lends itself well to acute pain indications where one or more nerves are treated before, during or shortly after an operation, so that the patient can go home without a device and still enjoy pain relief for a day or several weeks after the operation, for example after a replacement of joint or other orthopedic procedure. In other words, a device in which long-term direct contact with the target area or the nerve to be treated (for example via an implantable generator and a nerve sleeve) is not necessary. However, if desired and particularly for chronic pain indications, the device can still be implanted or partially implanted and/or taken home with the patient.
[0147] DEVICE EXAMPLE
[0148] Figure 1 provides a schematic representation of an exemplary electrical stimulation device 100. The electrical stimulation device 100 may be used to selectively and reversibly modulate targeted nerve or non-nerve tissue of a nerve structure with the application an electrical signal to treat a disease state of a patient. The stimulation device 100 includes an electrode 120 that delivers electrical stimulation at the treatment site, for example, that delivers the electrical stimulation at targeted nerve or non-nerve tissue of the nerve structure. Electrical stimulation can be delivered by a percutaneously placed lead (L) and a 120 electrode, by an implanted lead (L) and a 120 electrode, or by a 120 electrode advanced through a body opening and positioned adjacent (eg, near or in contact with) mucosal tissue overlying the targeted nerve structure (eg, sphenopalatine ganglion, Gasser's ganglion). An example in which the mucosal tissues include buccal mucosa, nasal buccal mucosa, gastrointestinal (GI) tract mucosa, bowel mucosa, bladder mucosa. Electrode 120 generates an electric field at the treatment site which results in selective and reversible modulation of nerve fiber activity to inhibit pain. As noted above, "modulation" of nerve fiber activity includes both excitation and inhibition/disruption of the passage of impulses along the neuron's axon in a nerve and may include the inhibition of nerve signal transmission to the point of creating a blocking effect.
[0149] The delivery of the electrical stimulation signal includes interactions with other nearby tissues. For example, in the case of percutaneous application and electrode placement, electrical signal stimulation is delivered via electrode 120 which has passed through and traveled through the patient's external tissues, including skin, fat, its bones and muscles, in order to place the electrode 120 in proximity to a target nerve structure. In this example, electrical stimulation influences not only the target neural structure, but also surrounding tissues such as connective tissue, nerve structure support tissues, fat, bone, muscle, and cardiovascular tissues such as those present in and around blood vessels. In the case of a transmucosal application, electrical signal stimulation is delivered via electrode 120 which is placed in proximity (e.g. near or in contact) with the overlying mucosal tissue. Electrical stimulation can affect the targeted nerve structure, as well as tissues below and around electrode 120, tissues interspersed between electrode 120 and the target nerve structure, and other surrounding tissues (including the skin, fat, muscle, bone, cartilage, connective tissue, nerve structure supporting tissues, cardiovascular tissues and cells such as those found in and around blood vessels, and other tissues present in the epidermis, dermis, as well as nerve receptors, hair follicles, sweat glands, sebaceous glands, apocrine glands and lymphatic vessels). Whereas the application of electrical stimulation at the site of treatment, in percutaneous and transnasal applications, will modulate (eg, selectively and/or reversibly) the targeted nervous or non-nervous tissue of the nervous system structure to inhibit the perception of pain, the electrical stimulation and stimulation device 100 is designed so as not to cause any damage to the structure of the nervous system and/or the surrounding tissue (eg, the overlying mucosal tissue).
[0150] As shown schematically in Figure 1, Stimulator 100 and Electrode 120/Leads L can be reused or disposable. Desirably, the nerve structure can be modulated via disposable L-wire and electrode 120, and driven by an external stimulator/reusable signal generator 140 and controller 130. It is contemplated that stimulation device 100, as a whole, can be sized and configured for implantation into the patient (under the patient's skin) at a location adjacent to the targeted nerve structure (N), shown schematically in Figure 2A. The power source 180, providing electrical energy to the controller 130/signal generator 140, can be positioned inside or outside the patient. It is also contemplated that only lead/electrode 120 be implanted in the patient and that the remaining components, including signal generator 140 and controller 130, be incorporated into a portable device that can be easily manipulated to deliver therapy, shown schematically in Figure 2B. It is further contemplated that stimulation device 100, including signal generator 140, controller 130, and leads/electrode 120 could be incorporated into a larger, non-portable device designed to remain on a fixed surface or on a cart that can be moved within the premises of a medical clinic, only 120/wire (L) electrodes are advanced percutaneously through an opening in the patient's skin or through another opening in the patient's body (for example, through the nasal cavity).
[0151] The stimulation device 100 can be used to reversibly and/or selectively inhibit pain while preserving other sensory function. Specifically, the electrical stimulation provided by the stimulation device 100 can reversibly and/or selectively modulate the nerve signal transmissions by the nerve fibers that are responsible for transmitting pain while preserving the nerve signal transmission by the nerve fibers. nerves responsible for other sensory and motor functions, and proprioception.
[0152] With respect to the reversibility of modulated nerve function, stimulation device 100 can reversibly inhibit pain, for example, by inhibiting or blocking nerve signal transmission for a period of from about 1 day to about 30 days. Preferably, pain perception is inhibited for a period of about 5 days to about 30 days. For chronic pain, pain perception is inhibited for a period of about 90 days to about 356 days. Reversibility of nerve signal transmission and subsequent recovery of function after appropriate post-treatment time is important, especially for acute post-operative pain. The stimulation waveform parameters can be adjusted to adjust the expected duration of pain inhibition and to ensure that pain inhibition does not last longer than desired. For example, in patients undergoing knee replacement surgery, it is important that pain perception returns 15 to 30 days postoperatively because acute sensations of pain are an important protective signal to help patients regulate their physical activity during recovery.
[0153] With respect to selectively modulated nerve function, stimulation device 100 can selectively modulate nerve or non-nerve tissue inhibiting pain perception and preserving other sensory and motor functions, as well as proprioception. This produces a scenario in which electrical neuromodulation treatment is selective for a subset of nerve structure functions while preserving other nerve structure functions. Pain perception is inhibited, while other sensory and motor functions and proprioception are preserved. For example, the electrical signal disrupts the transmission of pain signals from the periphery to the brain by inhibiting the transmission of the nerve signal by the nerve fibers responsible for the transmission of pain. This includes direct inhibition of pain signal transmission in neurons of the target neural structure or can be achieved by indirect inhibition of other downstream neurons responsible for pain signal transmission to the brain, such as the neurons of the central nervous system (for example, the spinal cord and the brain).
[0154] Preserved sensory function includes, for example, non-painful tactile sensation (low-threshold sensory function), vision, hearing, taste, olfaction and balance. It is also envisioned that the described electrical signal may modulate nerve signal transmission through nerve fibers responsible for transmission of thermoreception, autonomic activity, and visceral function.
[0155] Selective modulation of pain perception is particularly useful in cases where modulation must be applied to mixed nerve structures, such as peripheral nerves containing motor and sensory axons. For example, in many surgical procedures, it is desirable to modulate pain transmitted via mixed nerves to treat acute surgical pain, while preserving the motor, sensory, and proprioceptive functions of the nerve. Preservation of motor, sensory, and proprioceptive function when treating pain is especially important in cases where physical therapy or other movement of an appendix must be performed during recovery from surgery. For example, many post-surgical care programs include steps to help patients avoid muscle atrophy or other functional stagnation after surgery. Preserving control of motor and sensory and proprioceptive functions while treating pain can enable and enhance such programs.
[0156] As described in more detail below, one or more parameters of the electrical stimulation can be adjusted to selectively block nerve signal transmission through a selected type of nerve fiber and/or through a selected region of nerve structure. . Adjustable parameters of electrical stimulation include, for example, waveform, wave frequency, wave amplitude, electric field strength generated at electrode 120 (e.g., measured at electrode or treatment site), continuous wave offset, wave duty cycle (e.g. continuous delivery and/or intermittent delivery through the electrode), tissue temperature, parameter of the cooling mechanism (for example, a cooling rate, a cooling fluid flow rate, a cooling fluid pressure, a temperature measured at the treatment site or a part of the cooling mechanism) and a treatment duration . These parameters are adjustable and controllable through controller 130, user interface 170, and a cooling mechanism that may be incorporated into stimulation device 100, as described in more detail below.
[0157] For example, when the targeted nerve structure is a peripheral nerve, such as a large peripheral nerve such as those having a diameter greater than about 2.5 mm, electrical stimulation may inhibit nerve signal transmission through myelinated Aδ fibers and/or or the unmyelinated C fibers in the peripheral nerve, the electrical stimulation preserving the transmission of the nerve signal by at least one of the Aβ and Aα fibers, and/or the motor fibers. It is contemplated that at least one parameter of the electrical stimulation can be adjusted to selectively inhibit myelinated Aδ fibers and/or unmyelinated C fibers, while preserving nerve signal transmission by at least one of the Aβ fibers and Aα, and/or motor fibers.
[0158] In another example, electrical stimulation may inhibit nerve signal transmission through myelinated Aδ fibers and/or unmyelinated C fibers in the target peripheral nerve, whereby the electrical stimulation preserves nerve signal transmission through at least one of the fibers. Aβ and Aα, and/or motor fibers in a neighboring nerve or a neighboring nerve fascicle. By selectively blocking pain sensation while allowing nerve signal transmission through selected nerve fibers of nearby nerves and/or neighboring nerve fascicles, the vividness of pain sensation can be reduced, which prevents other fibers tall motor muscles to be affected.
[0159] In another example, the targeted nerve structure covered by a layer of mucous tissue, for example the Gasser's ganglion, the sphenopalatine ganglion (SPG). Electrical stimulation can be delivered through mucosal tissue to modulate unique nerve transmission by a particular type of nerve fiber to the underlying nerve structure and adjacent non-nerve tissue. Types of nerve fibers include, for example, parasympathetic nerve fibers, sympathetic nerve fibers, sensory nerve fibers). For example, when the targeted nerve structure includes the sphenopalatine ganglion (SPG), electrical stimulation selectively inhibits nerve signal transmission through parasympathetic nerve fibers including the SPG, sympathetic nerve fibers including the SPG, and/or sensory nerve fibers. including GSP. It is envisioned that this nerve signal transmission can be inhibited while also selectively preserving the function of at least one of the unselected nerve fiber types (e.g., parasympathetic, sympathetic, and sensory nerve fibers including the SPG).
[0160] It is further contemplated that at least one parameter of electrical stimulation can be tuned to differentially inhibit the function of myelinated Aδ fibers such that myelinated Aδ fibers exhibit a higher percentage of inhibited fibers than unmyelinated C fibers. . Nerve signal transmission via myelinated Aδ fibers is generally associated with the sensation of fast, sharp/throbbing pain, while nerve signal transmission via unmyelinated C fibers is generally associated with the sensation of dull/high-pitched pain. As a result, electrical stimulation can be tuned to differentially inhibit the function of nerve fibers responsible for acute pain sensation, such that these fibers have a higher percentage of inhibited fibers than nerve fibers responsible for pain sensation. deaf/high-pitched.
[0161] Likewise, it is further contemplated that at least one parameter of the electrical stimulation can be adjusted to differentially inhibit the function of unmyelinated C-fibers, such that unmyelinated C-fibers have a greater percentage of inhibited fibers than that of myelinated Aδ fibers. That is, electrical stimulation can be tuned to differentially inhibit the function of nerve fibers responsible for dull/high pain sensation, such that these fibers have a higher percentage of inhibited fibers than do nerve fibers responsible for a sensation of rapid, sharp, throbbing pain.
[0162] In another example, where the targeted nerve structure covered by a layer of mucosal tissue, such as the Gasser's ganglion or the sphenopalatine ganglion (SPG), electrical stimulation can be tailored to differentially inhibit parasympathetic nerve fiber function , sympathetic and/or sensory of the ganglion. For example, electrical stimulation delivered to the target site can differentially inhibit the function of parasympathetic nerve fibers in the SPG, with parasympathetic nerve fibers having a greater percentage of inhibited fibers than nonparasympathetic nerve fibers and nonnerve tissue. Similarly, electrical stimulation delivered to the target site can differentially inhibit the function of sympathetic nerve fibers in the SPG, with sympathetic nerve fibers having a greater percentage of inhibited fibers than nonsympathetic fibers and nonnerve tissue. Similarly, electrical stimulation delivered to the treatment site can differentially inhibit SPG sensory nerve fiber function, with sensory nerve fibers having a higher percentage of inhibited fibers than parasympathetic, sympathetic, and non-nerve tissue nerve fibers.
[0163] An additional mechanism of pain perception inhibition is when the inhibitory effect is downstream or secondary to the site of treatment. For example, when the targeted nerve structure is a large peripheral nerve, such as a nerve with a diameter greater than about 2.5 mm, electrical stimulation can modulate the activity or function of nerve or non-nerve tissues, which results in activation of a biochemical signaling cascade that causes decreased activation of spinal or cortical pain-representing neurons (e.g., via modulation of synaptic signaling), whereas nerve signal transmission by neurons of the central nervous system and the peripheral nervous system is involved in the detection, transmission, processing and generation of painless touch, motor control and proprioception are preserved. It is envisaged in this case that at least one parameter of the electrical stimulation can be adjusted to selectively inhibit the downstream or secondary effects of pain originating from the Aδ fibers and/or originating from the unmyelinated C fibers, while the function of the Central nervous system and peripheral nervous system neurons involved in sensing, transmitting, processing and generating painless touch, motor control and proprioception are preserved.
[0164] It is further contemplated in this case that at least one parameter of the electrical stimulation can be adjusted to differentially inhibit the downstream or secondary effects of pain from myelinated Aδ fibers, such that the downstream or secondary effects of myelinated Aδ fibers are more inhibited than the downstream or side effects of unmyelinated C fibers. Similarly, it is further contemplated in this case that at least one parameter of the electrical stimulation can be adjusted to differentially inhibit the downstream or secondary effects of pain from unmyelinated C-fibers, such that the downstream or secondary effects of unmyelinated C fibers are more inhibited than the downstream or secondary effects of myelinated Aδ fibers.
[0165] EXAMPLE OF ELECTRICAL STIMULATION
[0166] As described above, electrode 120 provides an electrical signal at the treatment site to selectively modulate nerve or non-nerve tissue by inhibiting pain perception and preserving other sensory and motor functions, as well as proprioception. The electrical signal disrupts the transmission of pain signals by modulating nerve or non-nerve tissue. Various parameters of the electrical signal can be adjusted, as shown below, to modulate function through the nerve structure, including, for example, a pulsed stimulation waveform (also referred to herein as a "waveform"), stimulation pulse rate (also referred to herein simply as "frequency"), stimulation pulse amplitude (also simply referred to as "amplitude"), electric field strength generated at electrode 120, wave shift in current continuous, wave duty cycle (eg, continuous delivery and/or intermittent delivery through the electrode), tissue temperature, cooling mechanism parameter, and treatment time. It is contemplated that some parameters may be adjusted individually to produce a desired effect, while others are adjusted in combination with some interdependence on each parameter adjustment within an effect to produce the desired effect. As described above and in greater detail below, various parameters and/or combinations of electrical signal parameters are adjusted to selectively and reversibly modulate nerve signal transmission through a selected type of nerve fiber and/or through a selected region of the nerve structure.
[0167] To facilitate selective and/or reversible inhibition of nervous system activities (eg, to block acute pain), the device and stimulation system are configured, in some embodiments, to deliver high frequency stimulation directly to the nerve and/or nearby tissue in order to invoke a sufficient pain inhibition response by the nervous system. High frequency stimulation can be applied in pulses during a single treatment/application and in a manner that does not damage nearby tissue and nerve tissue. It has been observed that high frequency stimulation applied at 500 kHz in a series of 20 millisecond pulses at up to 100 V for a few minutes (and up to a temperature of 42 C) can be applied to invoke a sufficient pain inhibition response that may selectively disrupt acute pain sensation but not affect other neurological functions such as motor control. It has also been observed that the same high frequency stimulation can be applied to invoke a reversible pain inhibition response as pain is blocked for a clinically relevant duration which can last from 1 to 30 days. Without wishing to be bound to any particular theory, it is hypothesized that the selective and reversible effect can be attributed to the particularly high voltage field of high voltage which is applied to the tissue without causing thermal damage to the treatment site, in especially in the nerves.
[0168] Figure 7A shows an example of electrical stimulation and the corresponding control parameters, which can be applied to the nerve and/or nearby tissue to selectively and/or reversibly inhibit nervous system activities, according to an illustrative embodiment . As shown in Figure 7A, electrical stimulation can be defined by control parameters such as amplitude, pulse duty cycle (including for example pulse envelope duration and inter-envelope interval), stimulation waveform and signal frequency. In addition to a pacing rate of 500 kHz, other pacing rate ranges can be applied. In some embodiments, the stimulation device and system are configured to deliver electrical stimulation having a stimulation frequency selected from the group consisting of about 100 kHz, about 150 kHz, about 200 kHz, about 250 kHz, about 300 kHz , about 350 kHz, about 400 kHz, about 450 kHz, about 500 kHz, about 550 kHz, about 600 kHz, about 650 kHz, about 700 kHz, about 800 kHz, about 850 kHz, about 900 kHz, about 950 kHz and about 1MHz. Application of electrical stimulation having a pulse duty cycle may produce a higher current amplitude or voltage and/or higher frequency (to generate a higher voltage field at the site treatment) without causing thermal damage to the fabric. The application of electrical stimulation having a non-sinusoidal waveform can be used to adjust the energy density applied in a given electrical stimulation and/or to also allow the application of a higher electrical field.
[0169] Figures 7B, 7C, 7D, 7E, 7F, 7G, 7H, 7I, 7J, 7K, 7L, 7M, 7N, 7O, and 7P each show a waveform for electrical stimulation, in accordance with an illustrative embodiment . As shown in Figures 7B-7F, in some embodiments, the stimulation waveform is a sine waveform (Figures 7B, 7G), a triangle waveform (Figure 7C), a square or rectangular waveform (FIG. 7D), a sawtooth triangular waveform (FIG. 7E) or a complex waveform (FIG. 7F).
[0170] In some embodiments, the frequency of a given pulse is changed (eg, as a chirp, as shown in Figures 7K, 7L, and 7M). In some embodiments, the electrical stimulation amplitude envelope is modified for a given pulse (Figures 7K and 7L).
[0171] In some embodiments, the electrical stimulation is a voltage controlled output. In some embodiments, the electrical stimulation is a current controlled output. In some embodiments, the electrical stimulation is a power controlled output.
[0172] In some embodiments, the stimulation waveform comprises a continuous load-balanced sinusoid (see, for example, Figures 7B - 7F, 7K, 7L, 7M, 7N, and 7P), or an additive combination of sinusoids ( for example, as a sinusoidal function (see Figures 7N, 7O and 7P).
[0173] The waves shown are merely illustrative. It is contemplated that other types of waveforms may be generated, such as pulses or other shapes. In some embodiments, the stimulation waveform comprises a single pulse having a duration of 1 to 10 μs.
[0174] Other stimulation pulse control parameters may be controlled, for example, in feedback mechanisms, such as electric field strength at the electrode, DC offset, tissue temperature, the parameter of the cooling mechanism and the duration of the treatment. In some embodiments, the stimulation device and system are configured to control electrical stimulation based on observed or measured temporal and/or spatial derivatives of voltage, current, power, and temperature (eg. example, the rate of change of temperature over time). In some embodiments, two or more of current-controlled stimulation, voltage-controlled stimulation, power-controlled stimulation, and temperature-controlled stimulation may be performed in combination to deliver nerve and non-nerve target tissue of the nerve structure. Amplitude, waveform, frequency, DC offset, duty cycle, and duration parameters can be set for stimulations such as current-controlled stimulation, voltage-controlled stimulation, power-controlled stimulation and/or temperature-controlled stimulation or a combination thereof.
[0175] Indeed, stimulation parameters can be optimized to selectively inhibit pain perception while preserving nerve activity responsible for motor activity, low-threshold sensory function, and proprioception. For example, stimulation parameters can be optimized to attenuate or abolish the activity of myelinated Aδ and unmyelinated C fibers while preserving (e.g., without attenuation) nerve activity in the nerve fibers responsible for motor activity, low-threshold sensory function or proprioception.
[0176] The amplitude and other parameters of the stimulation waveform can be adjusted to preferentially or optimally modulate activity in a desired region of a nerve (e.g., specific regions of a nerve versus to the complete cross-section of the nerve), as will be described in more detail below. The stimulation waveform may also include parameter changes that influence and reduce the apparent response (e.g., pulsating sensation at the nerve structure, motor response in a muscle adjacent to the target nerve, such as muscle spasm or muscle contractions) and activation of nerve tissue at the start of stimulation either at the start of the continuous waveform or at the start of each burst of stimulation during intermittent stimulation. Stimulation waveform parameters can also be adjusted to control the duration and time course of pain inhibition that will be achieved after treatment and to ensure that adequate pain inhibition is achieved with a single treatment.
[0177] The stimulation waveform parameters can be adjusted to allow treatment of larger nerves (e.g., greater than about 2.5 mm in diameter) and larger nerve structures or nerve structures of varying shapes and sizes. of different sizes, as well as neural and non-nerve tissue composition, for example by increasing amplitude or adjusting other parameters of the stimulation waveform that result in increased spatial size and shape of the electric field. Some nerve structures, such as the spinal cord and certain ganglia or plexuses, are large in nature and treatment of these large structures is made possible by adjusting the waveform parameters.
[0178] The stimulation waveform parameters can also be adjusted to enable non-damaging therapy and pain inhibition. Hardware and software may also be included to control the amount of direct current supplied simultaneously with the waveform. Controller 130 may include, for example, a current controller or a voltage controller to adjust the amount of direct current or voltage delivered simultaneously with the electrical signal.
[0179] The device and method of the present invention can be used to selectively and reversibly modulate nerve signal transmission, such as by inhibiting or blocking nerve signal transmission, to inhibit pain perception for a period of time. from about 1 day to about 30 days. Preferably, pain perception is inhibited for a period of about 5 days to about 30 days. Reversibility of nerve signal transmission and subsequent recovery of function after appropriate post-treatment time is important, especially for acute post-operative pain. The stimulation waveform parameters can be adjusted to adjust the expected duration of pain inhibition and to ensure that pain inhibition does not last longer than desired. In one example, the duty cycle, pulse amplitude, and treatment duration (see, for example, Figures 10 and 11) can be adjusted to produce a desired reversibility of nerve signal inhibition (see, for example , Figures 10 and 11). In another example, temperature control at the treatment site can be used to produce a desired selectivity of nerve signal transmission modulation (see, for example, Figures 10 and 11).
[0180] As mentioned above, the device and method of the present invention, including waveform parameters and their adjustment, can selectively inhibit acute pain (such as postoperative pain) for a period ranging from a few days to several weeks after the procedure. However, it should also be understood that the device and method of the present invention, including the waveform parameters and their adjustment, can also be used to provide therapeutic treatment for chronic pain pathologies. Therapeutic treatment of chronic pain may include continuous preventive delivery of signals, or abortive delivery on demand when episodes of chronic pain are experienced. This can be achieved by percutaneous, partially implanted and implanted approaches.
[0181] Compared to other methods of modulating the activity of a nerve structure using an electrical signal, the system and method of the present invention are capable of providing selective and reversible pain relief for periods of days. to a few weeks with a single treatment/application of the electrical signal. Other treatment modalities require repeated treatments over a period of days to provide significant and long-lasting pain relief, especially when it comes to treating large nerves. For example, pulsed radiofrequency, frequently used to treat pain in small nerves, uses intermittent pulses of a 45 V radiofrequency signal to stimulate the target nerve. Pulse is used in this case to avoid temperatures at the treatment site that could damage or destroy nerve tissue. Rather, the stimulation parameters of this description allow the application of a high voltage and frequency waveform that does not have the temperature limitations associated with a pulsed RF signal. Adjusting the stimulation waveform parameters allows control of the application of the electrical signal to ensure that adequate pain inhibition is achieved with a single application, while avoiding tissue damage.
[0182] For example, a system can be configured to deliver the electrical signal (also referred to as "electrical stimulation" in this description) at the treatment site with a frequency range of about 100 kHz to about 1 MHz, about 200 kHz to about 800 kHz, from about 400 kHz to about 600 kHz, and from about 450 kHz to about 550 kHz. In an exemplary system, the electrical stimulation delivered to the treatment site is at least 500 kHz. The electrical signal delivered to the treatment site has an amplitude range of ≥ 5 mA (peak-to-center, corresponding to 10 mA peak-to-peak) and ≤ 1.25 A (peak-to-center, corresponding to 2.5 A peak-to-peak ). In an example system, the electrical signal has an amplitude between 50 mA and 500 mA, 500 mA and 1 A, 1 A and 1.5 A, 1.5 A and 2 A, or 2 A and 2.5 A In an exemplary system where the electrical stimulation is delivered transmucosally, the electrical signal has an amplitude range between about 10 mA and about 5000 mA (peak to peak). The electrical signal delivered to the treatment site has an amplitude range of ≥ 10 V and ≤ 500 V (peak to center, corresponding to 20 to 1000 V peak to peak). In an example system, the electrical signal has an amplitude between 10 V and 1000 V, 20 V and 100 V, 100 V and 200 V, 200 V and 300 V, 300 V and 400 V, or 400 V and 500 V. In an exemplary system where electrical stimulation is delivered transmucosally, the electrical signal delivered to the treatment site has an amplitude range of ≥ 10 V and ≤ 1000 V (peak-to-peak). In an exemplary system, the electrical stimulation delivered to the treatment site has a power of between about 0.1 W and about 1250 W.
[0183] The electrical signal delivered to the treatment site may have a sine-shaped waveform, a square-shaped waveform, a triangular-shaped waveform, a frequency modulated waveform, a pulse (for example, an amplitude modulated waveform or a pulse waveform), and/or additive combinations thereof. An example of a frequency modulated waveform is a chirp. An example of an amplitude modulated waveform is a wavelet. In another exemplary system, the electrical signal delivered to the treatment site has an arbitrary waveform. In another example system, the electrical signal may have a combination of the previously mentioned waveforms. Repeated waveform delivery implies that a waveform is repeatedly delivered at a specified repetition rate. The electrical signal waveform can be delivered continuously or intermittently. Continuous delivery implies that the waveform is delivered at a specified waveform frequency continuously, without interruption. Intermittent delivery implies that the waveform is delivered at a specified waveform frequency during time envelopes separated by pauses during which no stimulation is delivered. For continuous dispensing, the duty cycle is 100% (for example, via the chirp function). For intermittent dispensing, the duty cycle is in the range of about 0.1% to about 99%, preferably 0.5% to 25%. The term duty cycle refers to a period during which the pulse has multiple oscillations with a predefined frequency. For intermittent distribution, the electrical signal has an inter-envelope width of about 1 ms to about 999 ms, preferably 70 to 999 ms, the inter-envelope width being defined as the time between the end of an envelope and the start of the next envelope. In one example, the electrical signal has a pulse width of 30 ms delivered at 10 kHz.
[0184] During an example of processing, the electrical signal is delivered for a processing time ≤ 30 minutes, preferably ≤ 15 minutes. In an exemplary system, the electrical signal is delivered for a treatment time ≤ 1 minute, from 1 minute to 5 minutes, from 5 minutes to 10 minutes, from 10 minutes to 15 minutes, from 15 minutes to 20 minutes, from 20 minutes to 25 minutes or 25 minutes to 30 minutes.
[0185] As described below, controller 130 is adjustable to apply electrical stimulation while maintaining tissue temperature between about 5°C and about 60°C. That is, the electrical signal may have a tissue temperature that has an amplitude between about 5°C and about 60°C.
[0186] The electrical signal delivered to the treatment site may be current controlled, voltage controlled, power controlled and/or temperature controlled. The electrical signal includes a continuous load-balanced waveform or pulse, or an additive combination thereof. Alternatively, the electrical signal comprises an uncharged balanced waveform or pulse, or an additive combination thereof.
[0187] The strength of the electric field generated at the target site is greater than 10 kV/m. The electrical stimulation delivered to the treatment site generates or induces an electric field strength at the target site and/or the electrode(s) of between about 20 kV/m and about 2000 kV/m. The electric field generated at the target site is between 20 kV/m and 2000 kV/m at its temporal peak, from 25 kV/m to 500 kV/m or from 50 kV/m to 400 kV/m. In a transmucosal application, the electrical stimulation generates or induces an electric field strength at the target site and/or electrode, preferably between about 20 V/m and about 1,000,000 V/m. The strength of the electric field varies depending on the distance from the electrode, the shape of the electrode, and other factors such as the conductivity of different tissues near the electrode. Tuning the waveform parameters of the stimulation waveform allows control of the spatiotemporal electric field within the tissue and at the interface of the electrode with the tissue. Tuning the waveform parameters of the stimulation waveform also allows control of the spatiotemporal thermal field within the tissue and at the interface of the electrode with the tissue. Spatiotemporal variations and levels of electric field and thermal field are important factors in producing the desired reversible selective inhibition of pain in target neural structures. Additionally, a cooling mechanism, as discussed in detail below, implemented in concert with the waveform and other aspects of the stimulation such as the electrode, allows control and reduction of the spatiotemporal thermal field independent or semi-independent of the electric field. Separating these two important variables ultimately allows for the delivery of a selective, reversible, and adjustable treatment that does not damage nerve tissue.
[0188] In addition to selective treatment of different fiber types, electrical stimulation and induced electrical field parameters as well as electrical waveform parameters can also be adjusted to preferentially modulate nerve signal transmission in a region. desired region of nerve structure, wherein the desired region of nerve structure is a portion of nerve structure less than its complete section.
[0189] Electrical stimulation may also be adjusted to reduce the apparent response (for example, a pulsing sensation at the nerve structure, a motor response in a muscle adjacent to the target nerve, such as a muscle spasm or twitch, and an activation of the nerve structure upon delivery of electrical stimulation to the nerve structure.
[0190] EXAMPLE OF COOLING MECHANISM
[0191] It is also contemplated that the stimulation device 100 may include a cooling mechanism to prevent damage to the patient's tissue when the electrical stimulation is administered. The cooling mechanism may be integrated with electrode 120 and/or a component separate from electrode 120 which may be coupled to the electrode or positioned at the treatment site separate from electrode 120. The cooling mechanism Cooling may be controlled by controller 130 or include a separate controller to direct its operation. The cooling mechanism is used to provide a cooling effect on the contact surface of the stimulation device 100 and/or on the contact surface of the electrode 120 and/or in the tissue near the treatment site.
[0192] It is apparent to those skilled in the art that delivery of electrical stimulation waveforms to tissue can result in heating of the tissue adjacent to the delivery electrode 120. When the heating of the tissue is excessive, thermal damage to the fabric level can be created. An object of the present invention is to produce a selective and reversible inhibition of pain perception while preserving other sensory and motor functions, as well as proprioception. Thermal tissue damage has been deliberately used to eliminate or inhibit the transmission of nerve action potentials. However, these approaches do not preserve sensory and motor functions, nor proprioception. Additionally, tissue cooling has been used with thermal ablations, for example with cooled radiofrequency ablations, to allow for increased power dissipation in the tissue, allowing for increased power of an RF waveform and the creation of a larger thermal lesion. However, these chilled RF approaches aim to raise the temperature of the tissue to at least 60-90°C in order to create a thermal injury in the tissue. In contrast, the present invention contemplates the use of a cooling mechanism that will preserve tissue below thermal damage levels while allowing the delivery of an electrical signal that can result in pain inhibition while preserving function. sensory, motor and proprioceptive nerve structure.
[0193] The cooling mechanism creates a cooling effect that prevents damage to patient tissue when electrical stimulation is delivered by keeping patient tissue temperatures below a tissue destructive temperature, for example, lower temperatures likely cause thermal damage to the fabric (for example by avoiding temperatures that exceed 42 to 45°C for several seconds). The cooling mechanism maintains the temperature of the contact surface of stimulation device 100 and/or electrode 120 below a tissue destructive temperature in response to feedback received from electrode 120 and/or a contribution from the patient and/or the operator. The feedback information includes measured temperature data received from a temperature sensor 210 coupled to the stimulation device 100. The temperature sensor 210 can measure the temperature of the contact surface of the electrode 120 and/or the temperature of the tissue of the patient adjacent to the contact surface of electrode 120. Temperature sensor 210 is electrically coupled to controller 130 and provides feedback information regarding the measured temperature. As described below, in response to the temperature feedback information, the operation of the cooling mechanism and/or the parameters of the electrical stimulation can be adjusted to control the temperature at the contact surface of the electrode 120, thereby reducing the temperature of the patient's adjacent tissue.
[0194] In one example, the cooling mechanism may include a pump that circulates a cooling fluid such as a pressurized gas or fluid (eg, carbon dioxide, nitrogen, water, propylene glycol, ethylene glycol, salt water or mixtures thereof) through electrode 120 via conduits 160 provided in leads (L) (see Figures 3A-3E). The circulating gas/fluid serves to remove heat from electrode 120, treatment site tissue, and surrounding tissue. This gas/fluid can be delivered at room temperature or can be cooled below room temperature using an incorporated gas/fluid cooling unit or using ice or other cooling mechanisms. Cooling of the gas/fluid can be carried out before and during the treatment. A thermally insulating coating or sheath may also be incorporated around the wires (L) to prevent heating of the coolant by heat transfer to the ambient environment.
[0195] In another example, the cooling mechanism includes a heat transfer material provided in contact with the tissue of the treatment site and/or the electrode 120. The heat transfer material may be disposed within the electrode 120/wires (L), on an outer surface of electrode 120 and/or on an introducer. The heat transfer material acts as a heat sink by removing heat from the electrode 120, treatment site tissue, and surrounding tissue. The heat transfer material may include a material with high thermal conductivity (eg a metal such as aluminum, a ceramic material, a conductive polymer), a material with a high heat storage capacity (eg a good mass heat, such as materials having a high specific heat capacity, a high heat capacity per unit mass, a high volumetric heat capacity and/or a high heat capacity per unit volume) and/or one or more Peltier effect circuits, or a combination thereof. The heat transfer material can also include a phase change material which can change phase at a temperature between about 40°C and 100°C. An example of a phase change material includes paraffin wax provided in a pathway that extends from the electrode 120/treatment site to ambient air. The heat exchange between paraffin wax and ambient air serves to remove heat from the 120 electrode/treatment site and surrounding tissues. Examples of additional cooling mechanisms are described in US application 62/403,876, filed October 4, 2016, entitled "Cooled RF Probes".
[0196] In addition to preventing tissue damage, the cooling mechanism allows for the selective inhibition of pain. For example, non-selective pain inhibition, in which non-painful or proprioceptive motor or sensory function is also inhibited, can be observed when temperatures are not below the desired threshold (such as 42-45°C during several seconds). Preserving the target tissue below such a thermal threshold by means of a cooling mechanism allows the selective inhibition of pain without modulating or inhibiting other functions of the nerve structure. Thus, electrode and tissue temperature is an important parameter that can be tuned by means of the cooling mechanism to allow selectivity of pain inhibition.
[0197] The use of the cooling mechanism also makes it possible to treat nerve structures of various shapes, sizes and compositions. For example, it may be necessary to increase the size of the spatial electric field generated by the electric waveform in the tissue to encompass larger nerve structures such as large peripheral nerves, cranial nerves, ganglia, nerves autonomic, parts of the spinal cord and the plexuses. One method to increase the size of the spatial electric field is to increase the amplitude of the electric waveform. The use of the cooling mechanism allows an electrical waveform to be delivered with a higher amplitude while maintaining the tissue at thermal levels preventing thermal damage. For example, when stimulation device 100 is treating peripheral nerves greater than 2.5 mm in diameter, use of the cooling mechanism allows adjustment of electrical waveform parameters, including amplitude, to levels high enough to treat the larger nerve target without causing thermal damage to the nerve structure. In another example, the nerve structure, such as the spinal cord or ganglia (e.g., Gasser's ganglion, sphenopalatine ganglion (SPG)), may be composed of and surrounded by various tissues with different thermal and electrical conductivities . In this case, the cooling mechanism enables the delivery of a therapeutic waveform that produces the desired selective and reversible inhibition of pain in a desired region of nerve structure, while preventing thermal damage to sites (including the nervous structure and its surrounding tissues) subject to heating.
[0198] Further, the use of the cooling mechanism makes it possible to adjust the spatial field of the tissue treated by the electrical signal in order to allow the modulation of the nerve signal transmission in a desired region of the nerve structure, the desired region of the structure nerve being a part of the nerve structure smaller than its complete cross-section. Cooling can be applied to tissues near electrode 120 or to tissues near the target treatment site to prevent tissue temperatures from exceeding a desired threshold level. For example, stimulation delivered through an electrode without cooling can produce a thermal field in the tissue that would be thermally damaging at certain locations in the tissue. The use and placement of the cooling mechanism at locations likely to cause thermal damage to the tissue allows non-damaging treatment and adjustment of the spatial field of the tissue treated by the electrical signal. In another example, thermal pulses in the tissue can be produced for short periods (eg, less than one second). The cooling mechanism allows the reduction of these thermal impulses below a threshold level at specific locations in the tissue to allow adjustment of the spatial field of the tissue treated by the electrical signal. In another example, the cooling and electrical waveform parameters can be adjusted simultaneously to allow treatment of a nerve structure (treatment of a portion of the nerve structure below its full cross-section or treatment of a complete cross-section of the nerve structure) without causing thermal damage.
[0199] EXAMPLE OF ELECTRODE
[0200] Figures 3A-3G provide schematic representations of various example electrodes 120 for delivering electrical stimulation to the target nerve structure. The electrodes 120 of Figures 3A-3E and 3G are in the form of one or more percutaneous electrodes configured to be placed in close proximity (e.g., the electrode is approximately 1 cm, approximately 5 cm or less 2 mm from the structure of the nervous system, without coming into contact with the structure of the nervous system), around and/or in contact with a target nerve. Examples of electrodes are illustrated in Figures 3A to 3E and 3G in a side perspective view. Examples of percutaneous electrodes are also described in U.S. Patent Application No. 15/501,450, filed February 3, 2017, entitled "Selective Nerve Fiber Block Method and System."
[0201] Each electrode used in a bipolar or multipolar manner comprises at least one anodic region and at least one cathodic region placed close to/in contact with the target nerve “N”. The unipolar electrode 120 shown in Figure 3A may include a cathode located near a nerve and a return electrode (eg, an anode) positioned some distance away (eg, as a patch electrode). on the surface of the skin). Bipolar and multipolar electrode configurations, as shown in Figure 3B, have at least one cathode and one anode near the nerve. The shape and size of the electrodes, as well as the spacing between electrodes, are specific to the contour of the electric field and the thermal fields surrounding and penetrating the nerve in order to allow selective and reversible modulation of the target nerve structure. Figure 3C provides another example of a percutaneous electrode 120 having a hook or J shape. As shown in Figure 3C, electrode 120 is sized and configured to conform to the target neural structure laterally in the convex portion of the hook shape, so that when positioned, the neural structure is retained near the electrode 120 and contact between the neural structure and the contacts of the electrode 150 is ensured. As shown in Fig. 3C, electrode 120 includes two electrical contacts, a first contact 150 provided on the curved hook/J-shaped distal end of electrode 120 and a second contact 150 provided on the elongate main body of the electrode. electrode 120. Such an electrode may be designed to be inserted through an introducer and such that the hook/J-shaped portion of the end of the electrode is bent inside the introducer. introduction, thus providing a reduced profile. Upon exiting the introducer, the curved portion of electrode 120 expands and curves around the surface of the nerve structure. Figure 3D illustrates an exemplary electrode 120 in which the tip of the electrode defines a generally hemispherical shape and provides a generally uniform nerve contact surface. The electrode may include a stretchable conductive surface which, when inserted through a small diameter introducer, is confined/non-stretchable and provides a reduced profile. Upon exiting the introducer, the expandable conductive surface expands to fit around the surface (or part of the surface) of the target neural structure. Figure 3E illustrates an exemplary electrode 120 having a V or U shape. As shown in Figure 3E, electrode 120 is sized and configured to be placed such that the target nerve structure is laterally positioned within the convex of the V/U shape. Once located at the treatment site, the nerve structure is positioned within the convex portion of electrode 120 to maintain contact with contacts 150 on longitudinally opposite sides of the nerve structure.
[0202] Figure 3G provides another example of a percutaneous electrode 120 having a distal end extending at an angle to the main body portion of the electrode 120. This bipolar configuration includes two electrical contacts 150 positioned along the elongated body of the electrode forming a cathode and an anode near the nerve (N). As in each of the electrodes shown in Figures 3A to 3E and 3G, the length of the electrical contacts can be between 1 and 50 mm, depending on the size of the nerve structure/target nerve. For example, the length of electrical contacts may range from about 1 mm to about 30 mm. In another example, the length of the electrical contacts can be between about 2 mm and about 20 mm. In another example, the length of the electrical contacts can be between about 2 mm and about 15 mm. In yet another example, the length of the electrical contacts can be between about 5mm and 10mm. It is contemplated that the length of each of the electrical contacts 150 included on an electrode 120/an elongated body of the electrode 120 may be the same or different. For example, each of the electrical contacts 150 shown on electrode 120 in Figure 3E are the same length to generate a coherent, uninformed electrical field with respect to the nerve. In the example electrode 120 shown in Figure 3G, the length of the electrical contacts 150 varies along the length of the electrode 120. In particular, the length of the distal electrical contact 150a located at the distal end 122 of the electrode 120 is greater than the length of the proximal electrode 150b (positioned along the main body 124 of the electrode 120 between the distal electrical contact 150a and a proximal contact end of the electrode 120). Typically, distal electrical contact 150a may be at least twice the length of proximal electrical contact 150b. In one example, the distal electrical contact 150a may be about 10mm long and the proximal electrical contact 150b may be about 4mm long. In another example, the surface of the distal electrical contact 150a and of the proximal electrical contact 150b can be adapted, while the length of the electrodes can be different. For example, if the proximal electrical contact has a greater circumference/circumferential width than the distal electrical contact, then the proximal electrical contact could achieve a suitable surface by having a shorter length than the distal electrical contact.
[0203] As shown in Figure 3G, electrode 120 has an elongated body in which the distal end 122 of electrode 120 extends at an angle to the longitudinal axis of the main body portion of the electrode. 120. It is contemplated that the angle of the distal end portion 122 can be between about 0 and about 50 degrees. The angle of distal end portion 122 is between about 5 and about 15 degrees relative to main body 124/major axis of electrode 120. Distal end portion 122 of electrode 120, above beyond the elbow, may extend in a straight line (as shown in Figure 3G). It is also contemplated that the distal end portion 122 may be curved or include a curved surface. As shown in Figure 3G, distal electrical contact 150a is located along distal end portion 122 and proximal electrical contact 150b is located along elongated main body portion 124 of electrode 120. In this orientation, distal electrical contact 150a is sized and configured to interface with the targeted nerve and proximal electrical contact 150b is sized and configured to be positioned adjacent subcutaneous tissue, eg, fat, fascia, muscle. In this configuration, tissue resistance between electrode 120/electrical contacts 150 is increased, resulting in higher voltages delivered and lower currents, with lower current delivery providing less tissue heating.
[0204] Figure 3F illustrates an exemplary electrode 120 for use in the treatment of nerve structure and any overlying mucosal tissue. Specifically, the electrode of Figure 3F is suitable for use in delivering electrical stimulation to the Gasser's ganglion and/or the sphenopalatine ganglion (SPG). The stimulation device includes an elongated body portion 220 sized and configured to be advanced through the patient's nostril and along the upper edge of the middle nasal turbinate. One or more electrodes 120 are provided at a distal end of elongated body portion 220. Electrode 120 has a contact surface having a size corresponding to a size of the SPG so that electrical stimulation delivered at the electrode 120 can simultaneously modulate the entire SPG and also provide even pressure on a mucosal layer near/overlying the SPG. In general, the contact area of the electrode 120 is between 1.57 to 56 mm ² . The width of the contact surface of the electrode 120 comprised between at least 1 mm and 6 mm. In one example, the electrode contact surface 120 has an elongated triangular, spiked ball, or flat half-ball or circular shape. As described above, the electrode in Figure 3F is designed to be advanced through the nasal cavity to a position adjacent to the sphenopalatine ganglion (SPG). As such, elongate body portion 220 ranges from 5cm long to 20cm long. The elongated body portion 220 has a contour corresponding to an upper edge of the middle nasal turbinate. To facilitate delivery and positioning, it is also contemplated that the elongated body portion 220 be made of a flexible material. Although not illustrated, it is contemplated that stimulation device 100 and/or electrode 120 could be sized and configured to be placed in the patient's mouth. For example, electrode 120 may be located on a mouthpiece fitted around the gums and teeth such that electrode 120 is positioned over the gum tissue (eg, gum line). The electrode 120 may be located on the mouthpiece so that when worn it is adjacent to at least one peripheral ganglion or nerve, including, for example, a lingual nerve, an alveolar nerve, and a buccal nerve.
[0205] As described above, electrode 120 may include one or more contacts 150 to deliver electrical stimulation to the treatment area/target nerve structure. A contact 150 is defined as a part of the electrode 120 intended to form the interface between the electrode 120 and the tissue at which the electrical stimulation is delivered (so as to generate an electric field in the tissue). Configurations of electrode 120 and contact 150 can be designed to maximize and direct electric field and current flow into the target nerve structure, and deliver a therapeutic dose of electrical stimulation to nerves of different sizes, shapes and of varying compositions, without undesirable stimulation of nearby tissues, while ensuring reliable placement of electrode 120 relative to neural structure for optimal therapeutic effect.
[0206] Relevant electrode design factors include number of contacts, size, geometry, orientation, material, electrolyte medium, mode of distribution (e.g., unipolar, bipolar, multipolar), and flow path. return. Adjustment and tuning of these factors allow the electric field and thermal field to be guided through the appropriate neural structure or part of the neural structure to produce selective and reversible pain inhibition. Additionally, the adjustment and tuning of these factors allows the electric field and thermal field to be directed through the appropriate neural structure or part of the neural structure to allow therapeutic treatment to be effectively delivered in a single application. and to adjust the time to reversibility of treatment effects. Tuning and adjustment of these factors also allows the electric and thermal fields to be modulated to treat the entire cross-section of large nerve structures such as large peripheral nerves (>2.5 mm in diameter), cranial nerves , ganglia, autonomic nerves, plexuses and spinal cord, as well as to treat parts of large and small neural structures. For example, the size and shape of electrical contacts or the number of electrical contacts can be adjusted to optimize surface contact with a large nerve. Also, the size and shape of the electrical contacts or the number of electrical contacts can be adjusted to optimize transmission by surface contact/electrical stimulation to nerve structure underlying mucosal tissue.
[0207] The number of electrode contacts, size, geometry, orientation, material, electrolyte medium, delivery mode (eg, unipolar, bipolar, multipolar), and return path can also be adjusted to avoid thermal damage to the fabric. These factors influence the thermal field produced by the electrical waveform, including the occurrence of thermal damage at certain locations of the tissue relative to the electrodes, and the adjustment of these factors, including adjustment in the context of the mechanisms of cooling and waveform adjustment, helps to avoid thermal damage to tissue.
[0208] For example, electrode 120 is sized and configured to maximize and direct the electric field created by electrical stimulation delivered to the target nerve structure. Electrode electrical contact 150 may have a surface area in the range of about 1 mm ² to about 100 mm ² to accommodate the sizes of electric and thermal fields that are required to provide therapeutic treatment to parts. small and large nerve structures, as well as the entire cross section of small and large nerve structures. Preferably, electrode contact 150 has a surface area in the range of about 2.5 mm ² to 45 mm ² . Electrical contacts that are too large may include portions of contact surface 150 that are not in contact with neural structure and, therefore, serve as a shunt pathway through which current can flow. When designing electrodes for the therapeutic treatment of a neural structure, shunt current is often discouraged because it increases the current needed to power the control device to produce the therapeutic effect. As shown in Figure 3G, electrical contact 150 may also define a smooth curvilinear shaped perimeter including, for example, circular or oval shaped contact surfaces. Sharp edges of straight shaped contacts, for example square or rectangular shaped contacts, can cause increased current densities and thermal heating. However, it is contemplated that straight shaped contacts 150 may be used when specifically sized and located on electrode 120 to take advantage of increased current densities and thermal heating. Thus, the dimensions and shapes of the electrical contacts are optimized based on the desire to target the delivery of the therapeutic electric field and the thermal field to the nerve structure while maintaining the necessary current flow from the controller to produce the therapeutic effects.
[0209] In another example, electrode 120 may include at least two contacts 150 that operate in a multipolar dependent manner to provide current direction and/or focus of the resulting electric field. In another example, electrode 120 includes at least two contacts 150 (e.g., two contacts 150 on the same electrode 120 or multiple electrodes 120 with their corresponding contacts 150) that operate independently. In this way, the electrical stimulation delivered by each of the electrodes 120 can be alternated so that the total electrical stimulation delivered to the neural structure is delivered in less (half) the time. Specifically, each of the separate electrodes 120 may deliver an intermittent electrical stimulation signal, the electrical stimulation of the first electrode being alternated with the electrical stimulation of the second electrode, e.g., an "on cycle" of the first stimulation delivery electrical stimulation occurs during an "off cycle" of the second electrical stimulation and an "on cycle" of the second electrical stimulation delivery occurs during an "off cycle" of the first electrical stimulation.
[0210] In another example, electrode 120 may include multiple electrode contacts 150 that can be selected to direct electric and thermal fields by selecting one or more electrode contacts 150 to be used as an anode and one or more other electrode contacts. to be used as a cathode. By selecting different combinations of electrode contacts, the shape and size of the electric field and the thermal field can be adjusted. For example, with respect to electrode 120 of Fig. 3G, distal and proximal electrical contacts 150a, 150b may be positioned on the same side of elongated body/electrode 120. As such, electrical contacts 150a, 150b do not do not deliver electrical energy circumferentially around the portion of the circumference of the elongated body electrode 120 without electrical contacts (for example, electrical contacts 150a, 150b do not deliver electrical energy circumferentially with respect to the short axis of electrode body 120), thereby providing voltage field shaping and current direction of the delivered electrical stimulation. A brief electrical stimulation test pulse can be delivered through a subset of contacts to determine nerve proximity and coverage, and multiple contacts can be added until sufficient contact with the nerve is verified ( for example, by monitoring the motor output of the leg by movement or electromyography).
[0211] A resistor may be placed in series with the electrical circuit of electrical contacts 150 of electrode 120. For example, with respect to electrode 120 of Figure 3G, a resistor may be placed in series with one or the two electrical contacts 150a, 150b. The resistor will increase the stimulation impedance and voltage delivered by generator 140 at or below the desired setpoint temperature (e.g. tissue killing temperature) and reduce stimulation current and thermal variations. Similarly, electrical contacts 150 can be constructed from high impedance or high capacitance material. For example, materials with higher impedance or capacitance than stainless steel or platinum can be used to reduce stimulation current and thermal variations while still allowing high level voltage delivery. This will further increase the pacing impedance and voltage delivered by generator 140 at or below the desired setpoint temperature (e.g., tissue destruction temperature) while reducing pacing current and thermal variations.
[0212] Generally, electrical stimulation may be delivered to the target nerve structure using an electrode 120 which may be in the form of a set of percutaneous electrodes to temporarily and selectively modulate nerve fiber activity in the target nerve structure. . For example, electrode 120 may comprise an electrode assembly in the form of a paddle, sleeve, cylindrical catheter, or a fine needle, wire, or probe configured to be introduced percutaneously through an opening in the patient's skin. In another example, intended for use in the treatment of head and facial pain (as described in more detail herein), electrical stimulation may be delivered to the target nerve structure via and an electrode 120 placed on mucosal tissue of a patient, for example, an electrical probe sized and configured to be advanced transnasally to a target site near the gasser's ganglion and/or the sphenopalatine ganglion (SPG).
[0213] Additionally, electrical stimulation may be delivered to the target nerve structure via an electrode 120 implanted in the patient, for example for the treatment of chronic pain. In this case, electrode 120 can be surgically implanted and can be placed in contact with or around the neural structure during a surgical procedure or during a minimally invasive implantation procedure. Electrode 120 can be attached to neural structure and surrounding tissue using sutures or anchoring structures constructed on the electrode that attach the electrode to neural structures or surrounding tissue.
[0214] Lead (L) includes means for transmitting electrical energy between electrical stimulation device 100 and electrode 120, for example via conductive wire or cable. The wire (L) can be directly attached to the electrode 120 permanently or can be attachable and detachable using a conductive connector. In this case, compatible connectors would be present on the electrode 120 and on the wire (L). The lead may be directly attached to electrical stimulation device 100/signal generator 140 permanently or may be attachable and detachable using a conductive connector. In this case, compatible connectors would be present on the electrical stimulation device 100/signal generator 140 and lead (L). The wire (L) may also include fluid/gas transmission paths, such as lines 160 used to transmit a fluid/gas used to cool the electrode(s) 120. Fluid transmission lines 160 may be connected to the wire (L). electrode 120 and cooling device directly or via attachable/detachable connectors. The wire (L) may also be contoured to provide an optimal shape for placement of the electrode 120, for example to allow navigation of the electrode in an ideal location near the nerve structure and to navigate around obstacles or of tissues presenting a partial barrier between the point of insertion and the target neural structure.
[0215] Lead (L) and electrode 120 can be placed using lead introducer tools, such as cannulas, guidewires, introducer needles, and trocars. Particularly for percutaneous placement, these lead and electrode introducer tools can be used to navigate through the skin and underlying tissues to a position close to the target neural structure. The introducer tool can also be used to allow introduction/placement of all necessary 150 contacts and other electrode components close to the target neural structure. Lead (L), electrode, and introducer tools allow electrode placement near large and small target neural structures, including peripheral nerves, cranial nerves, ganglia, autonomic nerves, plexuses, and the spinal cord, and also allow for proper interfacing between the electrode(s) and these target neural structures, which helps to produce selective and reversible inhibition of pain perception. The lead (L), electrode, and introducer tools also allow placement of the electrode 120 in cases of percutaneous use, such as for acute pain, and for implanted use, such as for chronic pain .
[0216] Figure 4A provides a schematic representation of an exemplary percutaneous electrode 120 (eg, Figure 3G) positioned adjacent to a target nerve structure, eg, a peripheral nerve through an opening in the patient's skin. The electrode may consist of a single needle-shaped rod with two electrical contacts 150. In this example, the distal electrical contact 150a serves as an active electrical contact near the target neural structure (N) and the electrical contact proximal 150b serves as a return electrode. As described above, the rod material of electrode 120 can be selected based on a desired thermal conductivity and/or thermal mass (e.g., to allow electrode 120 to play the role as a heat sink, which can allow treatment waveforms to be delivered with higher current or voltage without increasing tissue temperature). The electrode shaft material 120 can also be selected based on a desire for the probe to be visible by ultrasound imaging (eg, an echogenic material) or by fluoroscopic imaging.
[0217] The distance (A to B) between the surface of the skin and the proximal electrical contact 150b (return contact) can be optimized to reduce the risk of damage to the skin or subcutaneous tissue. For example, the distance A to B can range from about 0 to about 40 mm. In another example, the distance AB may range from about 0 to about 20 mm. In another example, the distance A to B may range from about 5mm to about 15mm. In another example, the distance A to B may range from about 10mm to about 15mm. The distance (C to D) between the proximal electrical contact 150b (return contact) and the curvature and/or the distance (C to E) between the proximal electrical contact 105b and the distal electrical contact 150a (active contact) is chosen to optimize treatment results, for example, by shaping the voltage field to be oriented preferentially towards the target neural structure, or for example by focusing thermal energy during pulses of the therapy waveform, for example by diverting thermal energy away from the target neural structure. In an exemplary system, the distances C to D and C to E will be between about 2 mm and about 50 mm. Preferably, the distances C to D and C to E will be between approximately 10 mm and approximately 30 mm.
[0218] The distance (C to D) between the proximal electrical contact 150b (return contact) and the curvature and/or the distance (C to E) between the proximal electrical contact 150b (return contact) and the distal electrical contact 150a (return contact) active) can be selected to allow treatment of different target neural structures from different depths on patients with different anatomical configurations (e.g. different thicknesses of muscle, skin and fat layers, different depths to target neural structures, etc.) . For example, the distance between the proximal electrical contact 150b (return contact) and the bend or distal electrical contact 150a (active contact) (C to D or C to E) can be selected so that the distal electrical contact can be placed 150a (active contact) near a variety of target neural structures on a variety of different patients with a variety of different anatomical configurations, but such as the distance (A to B) between the skin and the proximal electrical contact 150b (contact of back) is sufficient to allow effective energy delivery without damaging the skin or other subcutaneous tissue. In another example, the electrode can have an adjustable distance (C to D or C to E) so that the proximal electrode contact 150b (return contact) can be repeatedly placed in a desired anatomical location (eg. example, in the fat layer or at a fixed distance under the skin) regardless of the depth of the target neural structure.
[0219] The distance (F to G) between the distal electrical contact 150a (active contact) and the distal end of the electrode 120 can be chosen to reduce spatiotemporal thermal spikes when delivering the treatment waveform by avoiding current delivery via geometric structures on contact 150a can produce high current densities, such as a sharp pointed tip. Additionally, the distance (F to G) between the distal electrical contact 150a (active contact) and the tip of the electrode 120 can be selected based on design and manufacturing considerations such as the choice of material for the shaft. and the end of the electrode. For example, if the electrode shaft and tip are made of a conductive material and are electrically or continuously connected to the distal electrical contact 150a (active contact), then the distal electrical contact 150a (active contact) may also include the end of the electrode 120. (eg, because the insulation on the sharp end can be removed when penetrating through tissue). Conversely, if the rod and the end of the electrode are made of a non-conductive material and are not electrically coupled to the distal electrical contact 150a (active contact), the distance (F to G) between the active contact and the end of the electrode may be greater than 0 mm. The choice of this distance (F to G) can also be influenced by the desired echogenicity of different probe components. Additionally, the tip of the 120 electrode can be configured to be smooth, non-pointed, or blunt to minimize high current densities or overcome the risk of insulation stripping during insertion.
[0220] The angle (α) of the distal end 122 of the electrode 120 can be selected to allow the guidance of the contacts 150 towards the target neural structure (N) during insertion and placement of the electrode 120. This angle (α) also helps to direct the transmission of the therapeutic waveform towards the target neural structure, for example, directing the current flow through the target neural structure, causing the voltage field to be directed preferentially towards the target neural structure, and/or by focusing thermal energy during pulses of the therapeutic waveform towards the target neural structure.
[0221] The length (E to F) of the distal electrical contact 150a (active contact) can be chosen to cover the entire diameter of a target neural structure or to cover only part of the target neural structure (for example a fascicle or a group of booklets). In one embodiment, the length (E to F) of the distal electrical contact 150a (active contact) and the length (B to C) of the proximal electrical contact 150b (return contact) may be identical. In other embodiments, the length (B to C) of the proximal electrical contact 150b (return contact) may be greater than the length (E to F) of the distal electrical contact 150a (active contact). The longer proximal electrical contact 150b (feedback contact) can ensure that the current density at the feedback contact is lower than the active contact (distal electrical contact 150a) (for example if the surface of the feedback contact is greater than that active contact). The longer feedback contact (proximal electrical contact 150b) may also reduce the risk of heat at the feedback contact (proximal electrical contact 150b) or near skin and subcutaneous tissue. In another embodiment, the length (B to C) of the proximal electrical contact 150b (return contact) may be less than the length (E to F) of the distal electrical contact 150a (active contact). The longer active contact (distal electrical contact 150a) may increase the impedance of the therapy waveform circuit. A longer active contact (distal electrical contact 150a) can also be used to increase the voltage field at the active contact while maintaining or reducing the current delivered to the tissue or the thermal heating of the tissue. Notably, increasing the impedance of the therapy waveform circuit can also be achieved, in whole or in part, by adding a resistive element, as mentioned above, to the active or return path in the therapy circuit. electrode 120. A resistive element can be added in line with an electrical cable or an electrical routing element that connects to an electrical contact 150. The cable itself can also act as a resistive element in the circuit.
[0222] Figure 4B provides a schematic cross-sectional view of the electrode 120 and electrical contact 150 of Figure 4B. The active and/or return contact of the electrode 120 can also be oriented so as to have a contact arc length (β) completely circumferential (360°) or, as illustrated in FIG. 4B, a length of contact arc (β) only partially circumferential (<360°). In some embodiments, the length of the contact arc (β) is less than 180°. Reducing the length of the contact arc (β) can be used to further direct transmission of the therapeutic waveform to the target neural structure (N), for example by directing current flow through the target neural structure, by shaping the voltage field oriented preferentially towards the target neural structure and/or by focusing thermal energy during pulses of the therapy waveform toward the target neural structure. Additionally, reducing the length of the contact arc (β) may also help reduce the amount of current that flows through pathways in the tissue that do not include the target neural structure (e.g., shunt currents ) or to reduce the exposure of non-targeted neural structure tissue to the voltage field provided by the therapeutic waveform. These measures can reduce system power consumption and reduce risk to non-target tissues. In one example, the distal electrical contact 150a (active contact), closest to the nerve, has an arc length of less than 180° to reduce shunt currents and preferentially direct the current to the nerve, whereas the electrical contact proximal 105b (return contact), which is furthest from the nerve, has an arc length greater than 180°. In this example, using a longer arc length for the return electrical contact allows the surfaces of the two contacts to be matched while minimizing the length (longitudinal) of the return contact, which can allow for a distance optimum separation between the two contacts.
[0223] The thickness (t) of electrical contact 150 may also be specified to allow fabrication of electrodes 120 to a specified needle gauge while providing sufficient electrical contact mass to withstand the mechanical and electrochemical stresses of contact materials that may be experienced during the use of the electrode 120. For example, the thickness (t) of the electrical contact 150 can be between 0.01 mils and 50 mils.
[0224] A 126 electrode holder may be incorporated into the design to help secure the 120 electrode and minimize movement of the 120 electrode after placement is complete. For example, an electrode holder 126 can help stabilize the position of the distal electrical contact 150a (active contact) relative to the target neural structure (N) during delivery of the therapy waveform. An electrode holder 126 may also allow a user to deliver the therapy waveform without having to hold the electrode 120 in place for the duration of the waveform delivery. Lead (L) may include electrical leads and connectors of electrode 120 may be used to make an electrical connection to distal electrical contact 150a (active contact), proximal electrical contact 150b (return contact), and to a temperature sensing element 210 (eg TC- and TC+).
[0225] Echogenic features, such as laser etched or mechanically etched materials, can also be incorporated at desired positions on the electrode to allow for enhanced visualization under ultrasound imaging.
[0226] The temperature sensing element 210 (also called a temperature sensor) can be selected to provide a desired accuracy (e.g., +/- 2°C, or e.g., +/- 1°C, or e.g., + +/- 0.5°C or for example +/- 0.3°C) and a desired range (for example 0 to 100°C, or for example 20 to 80°C or for example 30 to 70°C). The accuracy of the thermocouple depends on the ambient temperature at the cold junctions as well as manufacturing factors. Additionally, temperature sensing element 210 and electrode 120 can be designed to provide a desired response rate in temperature measurements (e.g., a time constant of 0 to 500 ms, or a time constant 0 to 100 ms, or a time constant of 0 to 10 ms or a time constant of 0 to 1 ms). The shape/size of a thermocouple junction as well as the specific heat capacity of the materials used in the electrode 120 and the thermocouple/temperature sensing element 210 can be designed to produce a desired temperature measurement response rate .
[0227] Figure 10 illustrates various exemplary bipolar electrical contact 150/electrode 120 configurations. As will be described in more detail below, exemplary configurations A through D illustrate a single body electrode 120. FIG. Exemplary configurations E through H illustrate a single body electrode 120 having a concentric contact structure as described with respect to Figures 11A and 11B, electrode 120 used in conjunction with a windowed introducer cannula 230. Example configurations I through J illustrate a flexible electrode 120 used in conjunction with a curved introducer cannula 230. And example configurations K through M illustrate a straight electrode 120 used in conjunction with a straight introducer cannula 210. It is contemplated that any of these configurations, individually or in combination, could be used on any of the electrodes 120 described herein.
[0228] As will be described below, example configurations include single-body 120 electrode designs and multi-body 120 electrode designs. For example, configurations A through D and E through H illustrate examples of one-body salt configurations, consisting of a single electrode rod 120 comprising two electrical contacts 150. The end of the electrode 120 may be rounded and smooth (eg A, E to H) or pointed (eg B to D). The proximal electrical contact 150b (return contact) can be fully circumferential (eg, A and B) or partially circumferential (eg, C to H). The distal electrical contact 150a (active contact) can be shaped into a variety of different geometries for the purpose of including/excluding the tip of the electrode 120 as the electrical contact and/or directing the therapy waveform to the target neural structure. A lumen may be incorporated into all designs to allow injection of fluid through electrode 120. For example, the lumen may be used to deliver drug treatment to the treatment site (eg, pain medication) prior to , during and/or after delivery of the electrical stimulation. In example D, a sharp end is avoided as part of the active contact by using a second body that has no electrical contact. In this case, a sharp introducer needle protruding from the central lumen extending through electrode 120. Here, the sharp introducer needle may be removed after electrode 120 is placed or when one wishes to inject a fluid through the lumen. In Examples E through H, a cannula 230 which has no electrical contact is used to provide a pathway for the insertion of the single body electrode 120. This cannula 230 can be placed initially without the single body electrode, for example with the use of a sharp introducer needle. After placement, the introducer needle can be removed and the electrode 120 can be inserted into the cannula 230. The cannula 230 can be used to provide windowed access 232 to feedback or active contacts (e.g. , a windowed access to the feedback contact in examples E to F). The cannula can be curved or straight (curved for E to F, straight for G to H). The electrode can also be curved or straight (curved for G to H, straight for E to F).
[0229] Multi-body designs, such as the examples shown in I-M, are composed of multiple rods having electrical contacts 150. In these examples, the return electrical contact 150a is provided on the cannula 230 and a second body 234 with the active electrical contact 150b is inserted through the central lumen of cannula 230. A multi-barrel can be used to provide an electrode with an adjustable distance between the active and return electrical contacts. For example, second body 234 can be moved longitudinally within cannula 230 until a desired spacing is achieved between active and return electrodes 150b, 150a. Once in a desired position and orientation, the position of the second body 234 inside the cannula 230 is fixed.
[0230] Cannula 230 can be curved (eg, I through J) or straight (K through M). The electrode body 234 which includes the active electrical contact 150b can be curved (eg K to M) or straight (I to J).
[0231] As shown in Figure 10, the active and return electrical contacts 150b, 150a can be combined with various combinations of electrical contact arc lengths. For example, configurations A, B, I, K, and L include electrical contacts in which the active and return electrical contacts 150b, 150a extend around the majority of the circumference of the electrode 120 (e.g., more 180°, 270°, 360°). For example, configuration A illustrates an electrode 120 having active and return electrical contacts 150b, 150a extending around the entire circumference of the electrode 120. Configurations E through H, J, M provide examples of electrodes 120 wherein return electrical contact 150a extends around less of the circumference of the electrode than active electrical contact 150b. Likewise, the example configurations illustrate the active and feedback electrical contacts 150b, 150a combined with various combinations of shapes, for example, the J configuration where the feedback electrical contact 150a has a straight shape and the active electrical contact 150b has a curvilinear shape. Figure 10 also illustrates the combined active and return electrical contacts 150b, 150a of different lengths and contact circumferences, for example, configurations B and C provide an electrode where the return electrode 150a is shorter (along the longitudinal axis of the electrode 120) than the active electrode 150b. The J and M configurations provide an electrode where the return electrode 150a is longer than the active electrode 150b. Configurations I, K illustrate a probe where return electrode 150a has a greater circumference than active electrode 150b.
[0232] Figures 11A and 11B illustrate an example connection between electrode 120 and wire (L) electrically coupling electrode 120 to generator 140. The connection may be facilitated by the design of the proximal end of electrode 120 and /or an electrode connector 128 coupled to the proximal end of the electrode 120. a plurality of circumferentially shaped contacts are arranged as overlapping concentric surfaces around the long axis of electrode 120. For example, as shown in Fig. 6A, contact A is the outermost conductive surface, contact B is a internal conductive surface (facing the major axis of electrode 120), contact C is another internal conductive surface (facing away from the major axis of electrode 120) and contact D is the most conductive surface inner (o oriented towards the long axis of the electrode 120). The concentric surfaces may each be electrically connected to unique components of electrode 120 (e.g., active electrical contact (distal electrical contact 150a), return electrical contact (proximal electrical contact 150b), and/or temperature detection 210). The concentric surfaces may be separated by dielectric layers including, for example, electrically insulating materials and/or air provided between adjacent conductive surfaces. For example, a dielectric layer with a thickness between 0.01 mils and 50 mils may be provided between adjacent concentric surfaces. Needle gauge may vary along the 120 electrode shaft or may be constant to accommodate concentric designs. Additionally, the needle gauge can be selected to allow passage of light in addition to routing active, return, and temperature sensing electrical traces/circuits.
[0233] Lead (L) may include a compatible cable and/or connector for electrically coupling electrode 120 and/or electrode connector 128 to generator 140. Lead (L) cable/connector includes concentric surfaces (eg. example, A, B, C, D) of corresponding size and shape and configured to electrically mate with corresponding concentric surfaces of electrode 120/connector 128 and provide low and consistent electrical connectivity between generator 140 and electrode 120.
[0234] The concentric surfaces can be designed to compress or expand when appropriate mechanical pressure is applied, thereby allowing a reliable and precise fit between the wire (L) and the electrode 120. For example, the concentric surfaces provided on the wire (L) and/or electrode 120/connector 128 may include notches in some of the conductive surfaces or in the dielectric layers provided between the concentric surfaces. The notches allow controlled expansion of the concentric surface while maintaining constant contact with the mating surface of the 120 electrode (or wire (L)).
[0235] The concentric design of lead (L) and/or electrode may include a lumen to allow passage of fluid through and/or between lead (L) and electrode 120. For example, lead connector 128 may include a lumen extending within the innermost concentric layer (and/or between other concentric layers) allowing attachment of a syringe or tubing to connector 128 and injection of fluid through the innermost concentric layer or between other concentric layers.
[0236] Additionally, the concentric design can be adopted not only as a component of the connector, but also as a means of guiding the electrical circuits of the electrical contacts and temperature sensing elements from their terminal sites to the proximal end of the connector. electrode 120 for connection to generator 140. The concentric design, including conductive surfaces and dielectric layers, can also be used along electrode rod 120. Such a design lends itself to simple manufacturing and possibly the use of the rod of the electrode 120 to ensure the connection with the wire (L), that is to say without the use of a connector 128, as illustrated in Figure 6B .
[0237] Additionally, the type and thickness of material for the dielectric layers between the concentric surfaces, as well as the type and thickness of material for the conductive layers, can be selected to minimize capacitance and/or maximize impedance. between conductive layers (e.g., to reduce shunting and spurious) and maximize delivery of the therapeutic waveform to tissue while minimizing electrical generator power requirements).
[0238] One or more temperature sensors/thermal sensing elements 210 may be included on electrode 120 to provide feedback regarding electrode 120 and/or tissue temperature at specified locations. In one example, the temperature sensor(s) 210 are placed at locations which are believed to be the highest temperature sites, such as near locations of the highest predicted current density, this includes, for example, example, sharp pointed ends, contact edges, discontinuities or rapid spatial transitions between materials of different electrical conductivities. The choice of these temperature sensor placement locations can be determined based on modeling studies or in vitro or in vivo temperature measurements in tissues or in model media such as saline solutions, gel formulations conductors or egg whites. The temperature sensor traces can be guided in such a way as to reduce the level of electromagnetic interference introduced by the delivery of the waveform into the temperature sensing circuit.
[0239] In addition to the concentric arrangement, various other arrangements may be used to guide the active and return electrical contacts and thermal sensing elements from their terminal sites to the position where they connect to the wire (L) cable or generator140 , including, for example, guiding insulating wires, using dielectric layers with non-insulating wires, and printing electrical traces with electrically conductive ink, etc. Additionally, the materials used to guide the active and feedback contacts and thermal sensing elements from their terminal sites to the position where they connect to the wire (L) cable or generator 140 can be carefully selected to allow transmission. reliable and efficient electrical signals without contamination or bypass. It should also be noted that such approaches can be used in cases where multiple electrical contacts 150 or multiple thermal sensing elements 210 are used on a single electrode 120.
[0240] SIGNAL GENERATOR EXAMPLE
[0241] Electrical stimulation device 100 may include signal generator 140 coupled to electrode 120 and controller 130. Signal generator 140 produces the stimulation waveform, including waveform parameters stimulation described above. Signal generator 140 includes the software and hardware components necessary to produce the specified stimulation waveform(s) and to enable modulation of the stimulation waveforms by means of controller 130. Signal generator 140 includes also the ability to deliver stimulation to the nerve structure via electrode(s) 120 while electrically isolating electrode 120 and the patient from grounded circuitry and other ground connections, so that the patient is not grounded when the electrode(s) are inserted into the patient's body. This is achieved, for example, via inductors or optical isolators. Additionally, signal generator 140 may include capacitors, inductors, resistors, and other passive circuit components near the output of electrode 120 that provide load balancing, reduce DC offset, or provide otherwise the desired regulation of the waveform parameters described above. Additionally, feedback monitoring circuits can be incorporated to collect information regarding the delivered waveform (such as current, voltage, power) and temperature (monitored for example, via a temperature monitoring mechanism). temperature (eg, temperature sensor 210) at electrode 120 or otherwise in tissue). Cooling mechanism parameters such as fluid/gas cooling medium temperature, fluid/gas flow rate and pressure, rate of heat transfer from electrode 120 and/or surrounding tissue, etc. can also be collected.
[0242] EXAMPLE OF CONTROL AND POWER DEVICE
[0243] As generally described above, controller 130 directs the operation of stimulation device 100/signal generator 140 to deliver electrical stimulation to the target neural structure via electrode 120. Controller 130 /signal generator 140 is electrically coupled to a power source 180 which supplies electrical energy to the stimulation device 100/electrode 120. The power source 180 may comprise an isolated power supply, so that all System instruments can be powered by an isolated power supply 180 to protect them from ground faults and power spikes carried by the electrical circuit. The power source 180 can also include one or more batteries, used either for the main power supply or for the emergency power supply, which would make it possible to operate the device without connection to the electrical mains of the installation.
[0244] Specifically, controller 130 directs the operation of signal generator 140 to deliver an electrical stimulation signal to the target nerve structure. Controller 130 may have on-board memory to facilitate high-speed data capture, output control, and processing, as well as independent waveform sample rates and online analysis. These components of the controller collect the feedback data necessary to understand the waveform delivered through the electrode, as well as the parameters of the cooling mechanism and the thermal and electrical state of the tissue. This feedback allows such processing parameters to be adjusted to provide selective and reversible pain inhibition.
[0245] As schematically illustrated in Figure 1, the stimulation device may include one or more electrodes 120 connected by an electrical lead (L) to the controller 130 via the signal generator 140. The controller 130 may include logic controller and software designed to deliver the desired electrical stimulation to a patient. Controller 130 can also process analog and digital data and record waveform data and digital information from patient monitoring system 190 and can generate waveform outputs, analog outputs, and analog outputs. simultaneously for real-time control of electrical stimulation (real-time automatic control, or manual user control). For example, controller 130 may adjust electrical stimulation in response to feedback received from temperature sensors coupled to electrode 120 and/or stimulation device 100. For example, stimulation device 100/1 Electrode 120 may include a thermocouple to measure temperature at the stimulation device contact surface and/or electrode contacts, as well as patient tissue adjacent to the electrode contact surface 120. temperature sensors are coupled to controller 130 and provide feedback regarding a measured temperature at the stimulation device 100 contact surface and/or electrode 120 contact surface and/or at other locations in the fabric. The controller 130 or the user can then adjust a parameter of the electrical stimulation in response to the feedback, the parameters including, for example, a waveform, a wave frequency range, a range of wave amplitude, electric field strength generated at an electrode, DC wave offset, wave duty cycle (e.g., continuous distribution or intermittent distribution), tissue temperature, a cooling mechanism parameter and a processing time. Additional feedback signals that may be relayed or recorded by the controller or used for electrical signal feedback control include temperature, contact impedance, current, voltage, and electrical signal strength, other electrical signal parameters, information about the electrical field in the tissue, blood flow, skin conductance, heart rate, muscle activity (such as electromyography) or other physiological signals.
[0246] Feedback control of electrical stimulation is desirable to avoid causing tissue damage, to adjust the modulation sphere of electrical stimulation within the target neural structure, and to adjust the modulation sphere of electrical stimulation to target small and large nerve structures and a diversity of nerve structures such as peripheral nerves, cranial nerves, ganglia, autonomic nerves, plexuses and spinal cord. Feedback control of electrical stimulation is also desirable to allow temporal adjustment of reversibility of pain perception inhibition, to adjust selectivity for adequate pain inhibition, for example, with a single treatment.
[0247] Whether to adjust electrical stimulation to selectively modulate nerve signal transmission through a selected type of nerve fiber and/or through a selected region of nerve structure, the control and/or operation of the controller 130 may be adjusted as a parameter of the electrical stimulation based on measured feedback of inhibition of nerve signal transmission (e.g., confirmation of no or limited nerve signal transmission from/through target nerve) and/or measured temperature feedback at the treatment site and/or patient feedback regarding pain perception. Confirmation of no or limited nerve signal transmission can be obtained through intraoperative monitoring techniques, such as, for example, recorded EMGs, direct nerve recordings that demonstrate a change in fiber response to pain in latency and/or amplitude or burst area. Controller 130 and the user interface are also used to adjust stimulation waveform parameters and properties of the electrode configurations and cooling mechanism in response to feedback. For example, controller 130 is configured to vary the duty cycle and/or stimulation envelope duration of electrical stimulation in real time, during treatment, to maximize the voltage delivered to the treatment site without exceeding the temperature of the target tissue at the treatment site, i.e., a tissue-killing temperature. Also, in some embodiments, the controller is configured to vary the duty cycle and/or stimulation waveform envelope duration of the electrical stimulation in real time to maximize the delivered current. at the treatment site without exceeding the temperature of the target tissue at the treatment site, i.e. a tissue destructive temperature. Providing an immediate temperature sensitive feedback loop allows therapeutic voltage (or current) to be delivered to the target nerve structure for as long as possible without causing damage. By controlling the current, the user can more easily control the temperature of the fabric and the safety. Similarly, blood pressure control is correlated with treatment efficacy.
[0248] Alternatively, a user can manually adjust stimulation waveform parameters and properties of the electrode configurations and cooling mechanism in response to feedback provided via user interface 170.
[0249] EXAMPLE OF USER INTERFACE
[0250] The stimulation device 100 may further include a user interface 170 for receiving user input and providing input to the user (e.g., patient or healthcare professional). The user can help direct the operation of stimulation device 100 including changes to the electrical signal. User interface 170 may further include a display providing information to the user regarding stimulation device 100. For example, the display may provide information regarding the status of stimulation device 100, such as on/off. , the signal transmission mode, the parameter date regarding the electric signal, etc. User interface 170 may be an integral part of stimulation device 100. It is also contemplated that user interface 170 may be incorporated into a remote device that is electrically coupled (wired or wireless) to the stimulation device. For example, user interface 170 may be provided on an external tablet or phone. User interface 170 can be used to allow the user to actively control electrical stimulation parameters (in real time) in response to feedback from controller 130.
[0251] The system may also include patient monitoring system 190. Patient monitoring system 190 may be used in conjunction with stimulation device and user interface 170. Patient monitoring system 190 acquires, amplifies, and filters signals and sends them to controller 130 and/or user interface 170 for feedback. The monitoring system may include a temperature sensor coupled to an outer surface of the patient's skin to measure changes in body temperature at the patient's surface, a blood flow meter coupled to or inserted into the patient's skin, a a skin conductivity meter coupled to the patient's skin, a heart rate monitor to collect signals from an electrocardiogram corresponding to the patient's heart rate, and a muscle activity monitor to collect signals from an electromyography. A heart rate monitor may include separate electrocardiogram (ECG) electrodes coupled to an alternating current (AC) amplifier. A muscle activity monitor may include separate EMG electrodes coupled to an AC amplifier. Other types of transducers can also be used. As described, all physiological signals obtained with the patient monitoring system pass through a signal amplifier/conditioner. The parameters of the electrical stimulation may be adjusted in response to feedback received on the patient monitoring system 190 by the controller 130 or the user. For example, at least one parameter of the electrical signal may be adjusted by the controller 130 in response to feedback received from the temperature sensor, an impedance meter, the blood flow meter, the skin conductivity meter, the heart rate monitor and muscle activity monitor. Information regarding stimulation waveform and parameters as well as electrical and thermal properties of the tissue, electrode, and cooling mechanism may also be provided via user interface 170 and used to adjust at least one parameter. electrical stimulation or cooling mechanism or electrode configuration. The adjusted electrical signal parameter may include, for example, waveform, wave frequency range, wave amplitude range, wave envelope duration range (i.e. i.e. the period of time that stimulation energy is delivered ("on"), e.g., continuously delivered stimulation energy has a long envelope duration and pulsed stimulation energy has a short envelope), an electric field strength at the electrode, a DC wave offset, a wave duty cycle (e.g. continuous distribution, intermittent distribution), tissue temperature, a parameter of the mechanism of cooling and treatment time. Additionally, the configuration of the electrodes (eg, bipolar, multipolar, unipolar, alternating, etc.) can also be adjusted in response to feedback.
[0252] PROCESS EXAMPLE
[0253] The present invention relates to a method for the selective and reversible modulation of targeted nerve or non-nerve tissue of a nerve structure with a single application of electrical energy to inhibit a patient's perception of pain. The method of practicing the present invention begins by positioning the patient in a comfortable position. A heart rate monitor (ECG), muscle activity monitor (EMG), or other monitor can be used to measure the patient's response to the electrical stimulation signal. The patient can be monitored for a period of time to determine the baseline condition prior to the application of the electrical stimulation signal.
[0254] Then, the targeted nerve structure can be identified and located. If the electrical signal is to be delivered transcutaneously, the targeted nerve structure can be located using a stimulation device such as a nerve locator (e.g. Ambu® Ministim® Nerve Stimulator and Locator) , using electrode 120. The nerve can also be localized by passing low levels of stimulation energy signal through the stimulation device. A muscle contraction elicited by a stimulus in a distal muscle group with low stimulation amplitudes (single pulse) will indicate that the point of stimulation is close enough to modulate the transmission of the nerve signal.
[0255] The electrical stimulation device 100 is then positioned at the treatment site near the targeted nerve or non-nerve tissue of the nerve structure. Electrode(s) 120 can be placed near the nerve structure percutaneously or transnasally, or by open incision and implantation.
[0256] For example, electrodes 120 may be positioned percutaneously adjacent nerve structure through an opening in the patient's skin (S) (see, eg, Fig. 5). The (internal) electrodes 120/leads (L) are attached to an external stimulation device/signal generator 140, or may be attached to a portable stimulation device. Placement of the electrodes 120 percutaneously may include penetrating the skin and navigating the electrode 120 and/or lead (L) under image guidance (such as with ultrasound) to a location close to the target neural structure . Additional positioning tools may be used, such as cannulas, guide wires, introducer needles, and trocars, to allow for tissue navigation and eventual electrode placement close to the target neural structure.
[0257] Positioning of electrode 120 near the nerve structure may include delivery of initial electrical stimulation (i.e., low level electrical stimulation, <0.5 V) at the site of treatment via electrode 120 and measuring the voltage and/or current at electrode 120. Based on the measured voltage and/or current, the position of electrode 120 at the site of treatment (near the target nerve structure) is adjusted. Other initial electrical stimulation signals are delivered to the treatment site and the position of the electrode 120 is adjusted, iteratively until the measured voltage and/or current correspond to a threshold voltage and/or or a threshold current indicating that electrode 120 is positioned around the nerve at a location to deliver effective treatment.
[0258] When the electrical signal is delivered percutaneously, the method may further include positioning one or more return electrodes on the outer surface of the patient's skin. Each anode preferably has a surface in contact with the skin such that the surface of the anode in contact with the skin has at least the same surface (or a greater surface) than the contact surface of the stimulation electrode. One or more return electrodes may be placed on the skin at a distance from one or more stimulation electrodes sufficient to avoid shunts.
[0259] The method of practicing the present invention may further include the use of coupling means such as, for example, an electrically conductive liquid, gel or paste which may be applied to the skin in the event of a return electrode or arranged in a sheath surrounding the electrode. 120 or at the tip of the electrode 120 in the case of the percutaneous placed electrode 120 in order to maximize and direct the electric field, deliver the therapeutic dose of stimulation energy to small and large nerves and ensure reliable placement electrodes/nerves for optimal therapeutic effect. Alternatively and/or additionally, one or more skin moisturizers, humectants, exfoliants or the like may be applied to the skin for the purpose of improving skin conductivity and/or reducing skin impedance. Examples of conductive pastes include Ten20™ conductive paste from Weaver and Company, Aurora, Colorado, and ELEFIX conductive paste from Nihon Kohden with offices in Foothill Ranch, California. Examples of conductive gels include Spectra 360 electrode gel from Parker Laboratories, Inc., Fairfield, New Jersey, or electro-gel from Electro-Cap International, Inc., Eaton, Ohio. An example of an exfoliant that can be used to prep the skin prior to application of transdermal electrodes is Nuprep Skin Prep Gel from Weaver and Company, Aurora, Colorado.
[0260] In another example, the electrodes can be implanted into the patient adjacent to the treatment site and close to the target neural structure. The electrodes and stimulation device can be implanted at or near the target neural structure. In another example, the electrodes can be implanted at the treatment site, with the leads extending through the patient's skin to the stimulation device. It is also contemplated that the electrodes can be implanted at the treatment site and can be wirelessly activated through the patient's skin. It is also contemplated that a wireless receiver module could be implanted and used to receive wireless input from controller 130 and then communicate with the electrode via conductive wires.
[0261] Another example is the placement of electrode 120 (e.g., Figure 3F) into a nasal turbinate via a transnasal approach for transmucosal electrical signal delivery to the gasser's ganglion and/or sphenopalatine ganglion (SPG). For example, the electrode 120 and wire can be inserted into the patient's nose and placed in a nasal turbinate and held securely while delivering the electrical signal (see, eg, Figures 9A and 9B). A method may be used in which the patient's sneeze reflex is suppressed, for example, by using a chemical block or electrical nerve block or by intentionally evoking a sneeze reflex, then placing the lead and electrode immediately after the sneeze before the patient can generate a second sneeze reflex. The initial intentional sneeze reflex can be triggered by the wire and/or electrode or by a separate probe inserted into the nose. It is also contemplated that electrode 120 may be positioned adjacent to the Gasserian ganglion and/or the sphenopalatine ganglion (SPG) by a percutaneous approach. Whether through a transnasal or percutaneous approach, the position of the SPG can be initially localized using, for example, magnetic resonance imaging (MRI), fluoroscopy and ultrasound imaging.
[0262] Once the electrodes 120 are placed, traditional electrical stimulation can be delivered through the electrodes 120 to ensure sufficient tissue/nerve proximity, and impedance measurements can be collected and used in a similar manner. The stimulation device can then be programmed to optimize electrode contact selection, return electrode selection, and stimulation parameters, as discussed above. It is envisioned that the selection of optimal stimulation parameters may include delivering different candidate waveforms with different parameter configurations until an appropriate result is achieved. It is further contemplated that selection of optimal electrode contact 150 and return electrode configurations may include delivering electrical signals via different electrode contact 150 and return electrode configurations up to obtaining an appropriate result. These optimizations can be performed manually by the user or can be delivered by the closed-loop controller as part of an iterative algorithmic search or a pre-programmed search. If desired, a chemical nerve blocking agent can also be administered through the electrode wire prior to delivering the electrical signal. Chemical nerve blocking can help dampen the apparent response and improve patient comfort.
[0263] The stimulation electrical signal can then be delivered to the treatment site near the targeted nerve structure via the electrode(s) using one or more of the stimulation parameters described above. The controller 130, receiving a supply of electrical energy from a power source 180, can direct the operation of the stimulation device to provide an electrical signal sufficient to selectively modulate targeted nerve or non-nerve tissue inhibiting perception. the patient's pain while preserving other sensory and motor functions and proprioception. The user can also control the parameters of the electrical signal in real time in response to feedback provided through the controller 130 to the user interface 170. A single application of the electrical signal at the treatment site can modulate selectively target nerve or non-nerve tissue and then inhibit pain perception for a period of about 1 day to about 30 days.
[0264] Where the electrode comprises at least two electrodes which operate independently, it is contemplated that a first electrical stimulation signal may be delivered via the first electrode and a second electrical stimulation signal via the second electrode. The first and second electrical stimulation signals may be emitted intermittently, with the first electrical stimulation alternating with the second electrical stimulation. In this configuration, the activation cycle of the first electrical stimulation takes place during an off cycle of the second electrical stimulation. Similarly, the activation cycle of the second electrical stimulation takes place during an off cycle of the first electrical stimulation.
[0265] The perception of pain by the patient is inhibited because the application of the electrical signal at the treatment site selectively modulates the targeted nervous or non-nerve tissue modulating the transmission of the nerve signal by the nerve fibers responsible for the transmission of pain. During this time, the transmission of the nerve signal by the nerve fibers responsible for other sensory and motor functions and proprioception is preserved. “Other” preserved sensory functions include, for example, touch, vision, hearing, taste, smell and balance. Application of the electrical signal may also inhibit and/or disrupt nerve signal transmission through nerve fibers responsible for transmitting signals related to thermoreception, autonomic activity and visceral function.
[0266] In its simplest form, the method can rely on patient feedback regarding their perception of pain after delivery of the nerve-blocking stimulation signal to assess the effectiveness of temporary and selective nerve modulation. In some examples, patient sensations, such as heartbeat, tingling, heaviness, and/or deep pressure, experienced during stimulation can be used to direct various stimulation parameters, including voltage, current, pacing impedance and therapy duration (duty cycle and pacing duration; therapy duration and end of therapy; delivery (“on” pacing duration).
[0267] Alternatively and/or additionally, the method may rely on feedback collected by a recording electrode, such as an electrocardiogram, galvanic skin response, blood flow meter, skin or body temperature and/or signals from an electromyogram to assess the effectiveness of temporary and selective nerve modulation, since stimulation may occur before, during, or immediately after surgery, when the patient is unable to provide of comment.
[0268] The target nerve structure may include peripheral nerve (large or small), cranial nerve, ganglion, autonomic nerve, plexus, and spinal cord. Target neural structures may include a mixture of motor, sensory, and/or autonomic neurons, or may include only one type of neural activity (e.g., motor only, sensory only, autonomic only). Target ganglia may include dorsal root ganglia, sympathetic ganglia, parasympathetic ganglia, sphenopalatine ganglia, gasser's ganglia, plexus, and/or spinal cord. In one example, the target nerve structure includes a large peripheral nerve (greater than about 2.5 mm, for example) and the electrodes deliver an electrical signal to the nerve that selectively and reversibly inhibits nerve signal activity associated with the pain for a period of days to weeks, with preservation of nerve signaling associated with motor function, painless sensation, and proprioception. For example, electrodes 120 can deliver an electrical signal that selectively and reversibly inhibits nerve signal activity in smaller diameter nerve fibers associated with sensory function (pain) for a period of days to weeks, with little or no change in the functionality of larger myelinated fibers associated with motor function, painless sensation, and proprioception. In one example, application of the electrical signal to nerve and non-nerve tissues of the targeted nerve structure inhibits and/or disrupts nerve signal transmission by at least one of a myelinated Aδ fiber and/or an unmyelinated C fiber provided in the nerve, the electrical signal preserving the transmission of the nerve signal through at least one of the Aβ and Aα fibers and/or the motor fibers. In another example, various electrical signal parameters can be adjusted to selectively inhibit at least one of the myelinated Aδ fibers or unmyelinated C fibers, for example, to inhibit nerve signal transmission through the myelinated Aδ fibers while preserving the nerve signal transmission through unmyelinated C-fibers, and vice versa. In another example, various electrical signal parameters can be tuned to differentially inhibit nerve signal transmission/function of myelinated Aδ fibers, such that myelinated Aδ fibers exhibit a higher percentage of inhibited fibers than unmyelinated C fibers. . Similarly, various electrical signal parameters can be tuned to differentially inhibit nerve signal transmission/function of unmyelinated C-fibers, such that unmyelinated C-fibers exhibit a higher percentage of inhibited fibers than do myelinated Aδ fibers.
[0269] In another example, application of the electrical signal to nerve and non-nerve tissues of the targeted nerve structure modulates nerve and non-nerve tissue function in such a way as to produce downstream or side effects resulting in pain inhibition, while preserving motor, painless sensory and proprioceptive activity. For example, various electrical signal parameters can be tuned to selectively modulate function resulting in reduced pain from activity in myelinated Aδ fibers and/or unmyelinated C fibers, while preserving motor function, non-painful and proprioceptive sensory, such as that transmitted by the Aβ and Aα fibers, and/or the motor fibers. In another example, various electrical signal parameters can be adjusted to selectively modulate function resulting in reduced pain from activity in myelinated Aδ fibers or unmyelinated C fibers, for example, inhibiting pain from activity in myelinated Aδ fibers while preserving pain from activity in unmyelinated C fibers, and vice versa. In another example, various electrical signal parameters can be adjusted to differentially modulate function resulting in reduced pain from activity in myelinated Aδ fibers, such that pain from activity in myelinated Aδ fibers shows greater inhibition than pain from activity in unmyelinated C-fibers. Similarly, various electrical signal parameters can be tuned to differentially modulate function resulting in reduced pain from activity in unmyelinated C-fibers, such that pain from activity in unmyelinated C-fibers exhibits greater inhibition than pain stemming from activity in myelinated Aδ fibers.
[0270] In another example, certain electrical signal parameters can be adjusted to preferentially modulate nerve signal transmission/function in a desired region of the nerve structure. In general, the desired region is the part of the nerve structure comprising the sensory components responsible for transmitting the feeling of pain. For example, with respect to the femoral nerve, the topography of the femoral nerve indicates that parts of sensory components innervating the knee are collected together in one region of the cross section of the nerve. Accordingly, it is contemplated that the electrical signal may be adjusted to preferentially modulate nerve signal transmission through the portion of the nerve cross-section corresponding to these target sensory components.
[0271] The various modifiable parameters of the electrical signal include, for example, waveform, frequency, amplitude, waveform envelope duration, intensity, electric field strength, waveform offset wave (DC offset), continuous delivery, and/or intermittent delivery across electrode 120. For example, controller 130 adjusts the duty cycle and/or waveform envelope duration. real-time waveform to maximize the voltage delivered to the treatment site, without exceeding a target tissue temperature at the treatment site, for example by modulating the stimulation cycle and/or the stimulation envelope to maximize the voltage delivered to the treatment site in real time while ensuring that the tissue present at the treatment site does not exceed a tissue destructive temperature. Also, in some embodiments, controller 130 adjusts the duty cycle and/or waveform envelope duration in real time to maximize the current delivered to the treatment site, without exceeding the temperature of target tissue at the treatment site, such as by modulating the stimulation duty cycle and/or the stimulation envelope to maximize current without exceeding a tissue destructive temperature.
[0272] In another example, the stimulation amplitude of electrical stimulation can be gradually increased to a plateau. Gradually increasing the electrical stimulation may eliminate and/or reduce the magnitude of the sensations experienced by the patient upon delivery of the electrical stimulation (e.g., tingling sensation felt in the receptive field of the nerve when the energy of stimulation is continuous; intermittent tingling sensations felt when stimulation energy is delivered in pulses).
[0273] The disclosed method encompasses the inhibition of pain perception associated with acute pain (including operative pain, post-operative pain, traumatic pain), neuropathic pain, chronic pain, and head and neck pain. in the face. When the pain is acute pain, the process of selectively and reversibly modulating targeted nerve or non-nerve tissue to inhibit pain perception may include application of the electrical signal immediately prior to the surgical procedure. The electrical signal can also be applied intraoperatively and/or immediately after a surgical procedure to inhibit the perception of pain associated with the surgical procedure and recovery. The electrical signal can also be applied hours and/or days before a procedure. For example, the electrical signal can be applied at least 24 hours before a surgical procedure. Delivering the electrical signal prior to a procedure, such as a surgical procedure, helps reduce patient pain and discomfort while preparing the patient for the procedure. Electrical signal delivery prior to a procedure can also be configured to allow the maximum pain relief effect to occur at the time of the procedure. It is also contemplated to target multiple nerve structures to allow for more complete coverage of the target area. For example, when the pain is acute postoperative pain occurring after a knee replacement procedure (including a total knee replacement procedure), electrical stimulation may be applied to the femoral nerve, sciatic nerve, obturator nerve and lateral cutaneous nerve and nerve branches, or a combination thereof. In another example, when the pain is shoulder pain, electrical stimulation can be applied to the brachial plexus, axillary nerve, suprascapular nerve, and lateral pectoral nerve, or a combination of these. When pain is associated with a medical procedure and/or trauma to the arm and/or hand, electrical stimulation may be applied individually to the internal, ulnar, and radial nerves and/or the brachial plexus. When pain is associated with a medical procedure and/or trauma to the ankle and/or foot, electrical stimulation may be applied to the tibial, peroneal/sural, and saphenous nerves, or a combination thereof. When pain is associated with hip replacement surgery, electrical stimulation may be applied to the femoral, sciatic, or obturator nerve (for example, to the common obturator nerve before it branches into the anterior and posterior nerves) and/or to the plexus, or a combination thereof. When pain is associated with anterior cruciate ligament (ACL) repair, electrical stimulation may be applied to the femoral or sciatic nerve, or a combination of these.
[0274] When the pain is neuropathic pain or chronic pain, the method of modulating nerve or non-nerve tissue of the target nerve structure may include the user (such as a physician or patient) applying the electrical signal as part of a predefined schedule for preventive care and/or as needed by the patient to provide an on-demand bolus of therapeutic treatment/pain relief.
[0275] The method of selective and reversible modulation of targeted nervous and non-nervous tissues to inhibit the perception of pain can also consist in measuring, at the level of a temperature sensor 210, the temperature of the contact surface of the stimulation device 100 ( for example, the contact surface of the electrode 120) and/or the temperature of the patient's tissue adjacent to the contact surface of the stimulation device during delivery of the electrical signal. Feedback information about the measured temperature is sent to the stimulation device. If the feedback indicates that the temperature of the contact surface of the stimulation device is higher than a threshold temperature of the device and/or if the temperature of the patient's tissue is higher than a threshold temperature of the tissue, the stimulation device/ control device where the user can adjust the operation of the stimulation device and the parameters of the electrical signal and/or a cooling mechanism to produce a cooling effect and reduce the temperature at the contact surface and the tissue . Reducing the temperature of the contact surface and/or the patient's tissue prevents damage to the patient's tissue. In some examples, the system may include a cooling mechanism coupled and/or integrated with the stimulation device 100 and/or the electrodes 120. If the feedback indicates that the temperature of the contact surface of the stimulation device 100 is higher at a threshold device temperature and/or if the patient's tissue temperature is above a threshold tissue temperature, the stimulation device 100/control device 130 and/or the user can activate and control the operation of the cooling to cool the contact surface of the stimulation device 100/electrode 120, the cooling of the contact surface preventing damage to the patient's tissue when the electrical signal is delivered by keeping the patient's tissue temperatures below a tissue threshold temperature. Likewise, the stimulation device 100/control device 130 and/or the user can activate and control the operation of the cooling mechanism to maintain the temperature of the contact surface of the stimulation device 100/electrode 120. below a threshold temperature in response to feedback regarding the measured temperature received from the temperature sensor 210.
[0276] Once the electrical signal has been delivered and pain perception has been inhibited while preserving other sensory and motor functions, and proprioception, the percutaneous and/or transcutaneous electrodes 120 can be removed. While the implanted 120 electrodes (if any) can remain inside the body for later use and continued treatment.
[0277] Example 1
[0278] In this example, valid subjects were recruited from the community and consented to the study using IRB-approved consent forms. High-dose opioid users were excluded from the study. Two types of sensory assessments were performed at different times on each subject: 1) a mechanical vibration test to assess the subject's sensitivity to painless touch sensation, and 2) a pain-eliciting electrical stimulation test to assess the subject's sensitivity to an aroused pain. At the start of the first session, assessments of the mechanical vibration test and pain-inducing electrical stimulation were performed on each leg. These were called baseline assessments. The subject then received treatment using the electrical stimulation waveform via an electrode placed on the left leg percutaneously. After the treatment, the mechanical and vibration tests were again evaluated on each leg. Subjects returned at subsequent visits for testing of mechanical vibration and electrical pain stimulation.
[0279] Mechanical vibration test: Subjects wore surgical gowns and sat in a comfortable chair. The right leg was fixed in a straight position to a support with foam padding to limit movement. A vibration device was placed in contact with the skin within the distribution of the saphenous nerve. Vibration tests were then performed in which a series of two periods were applied to the subject, one comprising vibration via the vibration device and the other comprising no vibration. For each test, the choice of the period during which the vibration was triggered was determined randomly and the subject was asked to verbally indicate the period in which he thought the vibration had been delivered. If the subject chose the correct period, a new test was performed until the correct choice was made for three successive tests, after which the amplitude of the vibration was reduced for the next test. If the subject chose the wrong period, the next test was performed with a higher stimulation amplitude. In this way, the threshold amplitude was determined based on the combined performance of 3 series of 50 tests on each leg. The threshold amplitude was identified for each leg in each session.
[0280] Electrical Stimulation Test Inducing Pain: Electrical stimulation was delivered through sticky surface electrodes placed over the saphenous nerve near the medial malleolus. The stimulation duration was 1 ms for the single pulses. The amplitude of the stimulation was gradually increased until the subject perceived a sensation for the first time. The stimulation was then delivered in a train of 9 pulses at 500 Hz and the stimulation amplitude was gradually increased until the subject perceived a transition from painless to painful sensation. The pain threshold was identified via ascending and descending limit testing and the average pain threshold for that session was documented. This threshold was identified for each leg in each session.
[0281] Electrical stimulation treatment: The electrical stimulation treatment was administered in a single treatment to each subject on the left leg only. After the baseline mechanical vibration test and the baseline pain-eliciting electrical stimulation test, the subject was prepared for administration of the electrical stimulation treatment.
[0282] The subject was placed supine on a procedure table and the skin prepared at a site above the saphenous nerve several centimeters distal and medial to the tibial tuberosity. A surface return electrode was placed on the contralateral leg over the gastrocnemius muscles. Ultrasound was used to identify the saphenous nerve and a radiofrequency probe (22 gauge, 4 mm exposed tip) was inserted through the skin. The position of the active tip of the radiofrequency probe was manipulated as stimulation (1 ms duration, 2 Hz) was delivered at progressively lower amplitudes. The manipulation of the position of the probe was carried out until reaching a sensory threshold below 0.2 V.
[0283] The electrical stimulation treatment was then administered to the subject at 2 Hz, 20 ms, for 240 s. The stimulation amplitude was adjusted in real time to maintain a probe tip temperature of 42°C. After the stimulation was complete, the probe was removed and the subject again underwent a mechanical vibration test and a pain-inducing electrical stimulation test, referred to as Visit 0.
[0284] Subjects returned for follow-up assessment at subsequent visits. Vibration thresholds were plotted over time to assess the effect of electrical stimulation treatment on tactile sensation, such as sensation transmitted via large-diameter myelinated fibers. Pain thresholds were normalized to baseline and plotted over time to assess the effect of electrical stimulation treatment on pain sensations, such as sensations transmitted through small-diameter fibers.
[0285] Figure 10 shows time-normalized pain thresholds for five subjects who received electrical stimulation treatments lasting 240 s. The green line shows the average response for topical analgesics such as lidocaine or bupivacaine, which provide analgesia for less than a day. An increase in pain thresholds was evident for all subjects, indicating a decrease in pain sensitivity. Return to baseline was evident seven days after surgery.
[0286] Figure 11 shows mechanical vibration thresholds over time for the same five subjects (electrical stimulation treatments lasting 240 s). No systematic change in mechanical vibration thresholds was evident, suggesting treatment selectivity for pain perception. In addition, the results of a clinical examination did not indicate any sensory deficit of the treated leg.
[0287] These results suggest that electrical stimulation treatment selectively and reversibly increases the pain perception threshold via a treated nerve with full reversibility within 7 days of treatment.
[0288] EXAMPLE OF COMPUTER SYSTEM
[0289] Although methods and systems have been described in connection with preferred embodiments and specific examples, it is not intended that the scope be limited to the particular embodiments indicated, as the embodiments described herein are intended to be in all respects more illustrative than restrictive.
[0290] As used herein, the term "computing device" may include a plurality of computers. Computers may include one or more hardware components such as, for example, a processor, a random access memory (RAM) module, a read only memory (ROM) module, storage memory, a database, one or more devices input/output (I/O) and an interface. Alternatively, and/or additionally, the controller may include one or more software components such as, for example, a computer-readable medium comprising computer-executable instructions for performing a method associated with the exemplary embodiments . It is contemplated that one or more of the hardware components listed above may be implemented using software. For example, the storage may include a software partition associated with one or more other hardware components. It is understood that the components listed above are given by way of example only and are not intended to be limiting.
[0291] The processor may include one or more processors, each configured to execute instructions and process data to perform one or more computer-related functions to index images. The processor can be communicatively coupled to RAM, ROM, storage, database, I/O devices, and interface. The processor can be configured to execute sequences of computer program instructions to perform various processes. Computer program instructions can be loaded into RAM for execution by the processor. Herein, processor means a physical hardware device that executes coded instructions to perform functions on inputs and create outputs.
[0292] A processor can be a microcontroller, a microprocessor, or a logic circuit such as an ASIC (application specific integrated circuit), CPLD (complex programmable logic device), FPGA (user programmable field controller ) or any other programmable logic integrated circuit. In some embodiments, a processor is configured to execute an instruction stored in device memory.
[0293] The RAM and ROM may each include one or more devices for storing information associated with the operation of the processor. For example, a ROM may include a memory device configured to access and store information associated with the controller, including information to identify, initialize, and monitor the operation of one or more components and subsystems. The RAM may include a memory device for storing data associated with one or more processor operations. For example, a ROM can load instructions into RAM for execution by the processor.
[0294] The storage may include any type of mass storage device configured to store information that the processor may need to perform processes compatible with the disclosed embodiments. For example, the storage may include one or more magnetic and/or optical disks, such as hard disks, CD-ROMs, DVD-ROMs, or any other type of mass media device.
[0295] The database may include one or more software and/or hardware components which cooperate to store, organize, sort, filter and/or organize the data used by the controller and/or the processor. For example, a database can store hardware and/or software configuration data associated with hardware devices and I/O controllers, as described here. It is contemplated that the database may store additional and/or different information to that listed above.
[0296] I/O devices can include one or more components configured to communicate information to a user associated with the controller. For example, I/O devices may include a console with an integrated keyboard and mouse to allow a user to manage an image database, update associations, and access digital content. I/O devices may also include a display including a graphical user interface (GUI) for outputting information to a monitor. I/O devices may also include peripherals such as, for example, a printer to print information associated with the controller, a user-accessible disk drive (e.g., USB port, floppy disk, CD-ROM or DVD-ROM drive, etc.) to allow a user to input data stored on a portable media device, microphone, speaker system or other type of interface device appropriate.
[0297] The interface may include one or more components configured to transmit and receive data over a communications network, such as the Internet, local area network, peer-to-peer workstation network, direct-link network, wireless network or other suitable communication platform. For example, the interface may include one or more modulators, demodulators, multiplexers, demultiplexers, network communication devices, wireless devices, antennas, modems and any other type of device configured to enable data communication via a communication network .
[0298] Unless expressly stated otherwise, it is not intended that any of the processes presented herein be construed as requiring that its steps be performed in any specific order. Therefore, if a method claim does not actually recite an order to be followed or if the claims or the description do not otherwise specify that the steps should be limited to a specific order, it is in no way intended that an order can be inferred in any respect. This applies to any possible non-express basis for interpretation, including: questions of logic regarding the arrangement of steps or operational flow; simple meaning derived from grammatical organization or punctuation; the number or type of embodiments described in the description.
[0299] Throughout this application, various publications have been referenced in order to describe more fully the state of the art to which the methods and systems relate.
[0300] It is obvious to those skilled in the art that various modifications and variations can be made without departing from the scope or the spirit of the invention. Other embodiments will occur to those skilled in the art from consideration of the specification and practice disclosed herein. It is intended that the description and examples be considered exemplary only, only the claims below indicating the true scope and spirit of the invention.

权利要求:
Claims (11)
[0001]
A system for selectively and reversibly modulating targeted nervous or non-nervous tissue of a nervous system structure, the system comprising: an electrical stimulation device comprising one or more electrodes that are operable to deliver electrical stimulation at a treatment site proximate to targeted nervous or non-nervous tissue of the nervous system structure; and a controller configured to connect to one or more electrodes of the electrical stimulation device and to a power source to supply electrical energy to the electrode(s), the controller configured to direct operation of the device of electrical stimulation and apply the electrical stimulation at the treatment site through the electrode(s) to provide selective modulation of the targeted nerve or non-nerve tissue inhibiting pain and preserving other motor and sensory functions, as well as proprioception .
[0002]
2. The system of claim 1, wherein the electrode(s) are of suitable size and shape to be positioned adjacent to nervous system structure comprising at least one of a peripheral nerve, a cranial nerve, a ganglion, and a autonomic nerve, a plexus and the spinal cord.
[0003]
3. A system according to any of claims 1 or 2, wherein at least one of the electrode(s) has a size and shape and a contact surface configuration which are sufficient to deliver electrical stimulation to the nerve or ganglion. and wherein the controller is configured to generate an appropriate waveform forming the electrical stimulation to modulate the targeted nervous or non-nervous tissue of the nervous system structure.
[0004]
A system according to any of claims 1 to 3, wherein the controller is configured to direct operation of the electrical stimulation device to vary the electrical stimulation based on measured feedback selected from the group consisting of by: the measured inhibition of nerve signal transmission, the measured temperature, a contribution from the patient, a feedback corresponding to at least one of the adjustable parameters, a treatment setting associated with a recovery time, a contact impedance of the electrode, an electric field generated in the tissue, a patient's physiological response, and a combination thereof.
[0005]
5. A system according to any one of claims 1 to 4, wherein the controller is configured to direct operation of the electrical stimulation device to vary at least one parameter of the electrical stimulation to modulate transmission of the nerve signal via i) at least one of the myelinated Aδ fibers and/or the unmyelinated C fibers or ii) a large nerve or a large ganglion or a large neural structure, wherein the at least one parameter is selected from the group consisting of waveform, wave frequency, wave amplitude, wave envelope duration, electric field strength generated at electrode(s), DC wave offset, wave duty cycle, tissue temperature, cooling mechanism parameter, and treatment time.
[0006]
6. A system according to any one of claims 1 to 5, wherein the controller is configured to direct operation of the electrical stimulation device to deliver electrical stimulation at the treatment site having a frequency selected from a range of frequencies from 100 kHz to 1 MHz, from 200 kHz to 800 kHz, from 400 kHz to 600 kHz and from 450 kHz to 550 kHz, wherein the electrical stimulation delivered to the treatment site includes at least one of: an amplitude range between 5 mA and 1.25 A, an amplitude range between 10 V and 500 V, a power range between 0.1 W and 1250 W, and an electric field intensity at the target site and/or the electrode(s) of between 20 kV/m and 2000 kV/m.
[0007]
7. System according to any one of claims 1 to 6, in which the electrode or electrodes are sized and/or shaped to maximize and direct the electric field towards the structure of the nervous system, wherein the electrode or electrodes comprise at least two electrical contacts, wherein each of the electrical contacts has a length between 1 and 50 mm, preferably a length between 2 mm and 20 mm, a length between 2 mm and 15 mm, or 5 mm and 10 mm.
[0008]
8. System according to any one of claims 1 to 7, further comprising: a temperature sensor coupled to the stimulation device for measuring a temperature of at least one of i) a contact surface of the stimulation device and ii) patient tissue adjacent to the contact surface or electrode, in wherein the temperature sensor is coupled to the controller and provides thermal feedback regarding a measured temperature, and a cooling mechanism configured to provide a cooling effect at the treatment site to prevent damage to the treatment site, wherein the controller is adjustable to vary at least one parameter of the electrical stimulation in response to thermal feedback received from the temperature sensor.
[0009]
A system according to any of claims 1 to 8, wherein the controller is adjustable to apply the electrical stimulation to differentially inhibit the function of myelinated Aδ fibers or nerve fibers responsible for acute pain sensation /throbbing such that myelinated Aδ fibers and/or nerve fibers responsible for a sharp/throbbing pain sensation have a higher percentage of inhibited fibers than unmyelinated C fibers.
[0010]
A system according to any of claims 1 to 9, wherein the controller is adjustable to apply the electrical stimulation to differentially inhibit the function of unmyelinated C-fibers or nerve fibers responsible for pain sensation deaf/high-pitched such that unmyelinated C-fibers and/or nerve fibers responsible for dull/high-pitched pain sensation have a higher percentage of inhibited fibers than myelinated Aδ fibers.
[0011]
A system according to any of claims 1 to 10, wherein the electrode(s) comprise an electrode assembly in the form of an elongated body, the distal end of the elongated body including a curvature such that a portion of the distal end of the elongated body extends at an angle relative to a longitudinal axis of the elongated body, the angle of the distal end portion relative to the longitudinal axis of the elongated body being between 0 and 50 degrees, preferably between 5 and 15 degrees.

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引用文献:

---

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

---

---

US5983141A|1996-06-27|1999-11-09|Radionics, Inc.|Method and apparatus for altering neural tissue function|

---

US8060208B2|2001-02-20|2011-11-15|Case Western Reserve University|Action potential conduction prevention|

---

US20060052836A1|2004-09-08|2006-03-09|Kim Daniel H|Neurostimulation system|

---

US8983628B2|2009-03-20|2015-03-17|ElectroCore, LLC|Non-invasive vagal nerve stimulation to treat disorders|

---

US8352026B2|2007-10-03|2013-01-08|Ethicon, Inc.|Implantable pulse generators and methods for selective nerve stimulation|

---

US20090204173A1|2007-11-05|2009-08-13|Zi-Ping Fang|Multi-Frequency Neural Treatments and Associated Systems and Methods|

---

JP5385582B2|2008-10-10|2014-01-08|大学共同利用機関法人自然科学研究機構|Pain sensory nerve stimulator|

---

CN102202729B|2008-10-27|2014-11-05|脊髓调制公司|Selective stimulation systems and signal parameters for medical conditions|

---

EP2243510B1|2009-04-22|2014-04-09|Nevro Corporation|Sytems for selective high frequency spinal cord modulation for inhibiting pain with reduced side effects|

---

EP2646107A2|2010-12-01|2013-10-09|Spinal Modulation Inc.|Agent delivery systems for selective neuromodulation|

---

AU2012255073B2|2011-05-19|2016-06-30|Neuros Medical, Inc.|High-frequency electrical nerve block|

---

US8700180B2|2011-06-23|2014-04-15|Boston Scientific Neuromodulation Corporation|Method for improving far-field activation in peripheral field nerve stimulation|

---

AU2012304370B2|2011-09-08|2016-01-28|Nevro Corporation|Selective high frequency spinal cord modulation for inhibiting pain, including cephalic and/or total body pain with reduced side effects, and associated systems and methods|

---

US20130085548A1|2011-10-03|2013-04-04|Eugene Y. Mironer|Method of treating chronic pain in a patient using neuromodulation|

---

US8843209B2|2012-04-27|2014-09-23|Medtronic, Inc.|Ramping parameter values for electrical stimulation therapy|

---

US9919148B2|2012-05-25|2018-03-20|Boston Scientific Neuromodulation Corporation|Distally curved electrical stimulation lead and methods of making and using|

---

US9174053B2|2013-03-08|2015-11-03|Boston Scientific Neuromodulation Corporation|Neuromodulation using modulated pulse train|

---

US9242085B2|2013-06-28|2016-01-26|Boston Scientific Neuromodulation Corporation|Transcutaneous electrical stimulation for treating neurological disorders|

---

US10086201B2|2013-10-09|2018-10-02|GiMer Medical Co., Ltd.|Electronic stimulation device, method of treatment and electronic stimulation system|

---

US9526889B2|2013-10-09|2016-12-27|GiMer Medical Co., Ltd.|Electromagnetic stimulation device for changing nerve threshold|

---

EP3185951A2|2014-08-26|2017-07-05|Avent, Inc.|Selective nerve fiber block method and system|

---

US20160287112A1|2015-04-03|2016-10-06|Medtronic Xomed, Inc.|System And Method For Omni-Directional Bipolar Stimulation Of Nerve Tissue Of A Patient Via A Bipolar Stimulation Probe|

---

US10675468B2|2015-09-18|2020-06-09|Medtronic, Inc.|Electrical stimulation therapy for inducing patient sensations|

---

US10549099B2|2016-04-29|2020-02-04|University Of Utah Research Foundation|Electronic peripheral nerve stimulation|

---

US20190282267A1|2018-03-15|2019-09-19|Avent, Inc.|Percutaneous lead placement assembly|

---

GB2583551A|2018-12-07|2020-11-04|Avent Inc|Device and method to selectively and reversibly modulate a nervous system structure to inhibit pain|GB2583551A|2018-12-07|2020-11-04|Avent Inc|Device and method to selectively and reversibly modulate a nervous system structure to inhibit pain|

---

WO2022045530A1|2020-08-28|2022-03-03|재단법인 오송첨단의료산업진흥재단|High-frequency surgical apparatus and system for nerve blocking|

---

CN112023265B|2020-09-28|2022-01-07|杭州神络医疗科技有限公司|Electrical stimulation device|

法律状态:
2020-10-13| PLFP| Fee payment|Year of fee payment: 2 |

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2021-09-30| PLFP| Fee payment|Year of fee payment: 3 |

优先权:

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申请号 | 申请日 | 专利标题

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US201862776908P| true| 2018-12-07|2018-12-07|

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US62/776,908|2018-12-07|

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