JP6905524B2 - A system for treating neuropathy using electrical nerve conduction blocks - Google Patents

Description

Detailed description of the invention

(Government investment)
This study was, at least in part, funded by the National Institutes of Health, National Institutes of Health, National Institutes of Health and Stroke, with funding numbers R01-NS-074149 and funding numbers R01-EB-002091. Supported. The United States Government has certain rights to the invention.

(Related application)
This application claims the rights of a US patent with application number 14 / 969,826, filing date December 15, 2015, the entire contents of which are incorporated herein by all purposes.

The present disclosure relates to an electrical nerve conduction block (ENCB) as a whole, and more specifically to a system that does not produce damaging electrochemical reaction products and uses ENCB to treat neuropathy.

Many neuropathy is characterized by abnormal conduction in one or more nerves, resulting in unwanted nerve activity. In some cases, abnormal conduction relates to pain, spasms or other pathological effects achieved by different end organs. Examples of neuropathy include stroke, brain injury, spinal cord injury (SCI), cerebral palsy (CP) and multiple sclerosis (MS), and cancer, joint replacement, endometriosis, hyperhidrosis, dizziness, saliva. Includes secretion, torticollis, neurological tumors, saliva, etc. Traditionally, these neurological disorders have been treated with drugs or invasive methods such as Neurolies. Although these neuropathy are not commonly used clinically, the application of radio frequency alternating current (HFAC) and / or direct current (DC) waveforms blocks conduction in peripheral axons to stop unwanted neural activity. It can also be treated by.

HFAC waveforms have been shown to provide local, immediate, complete and reversible conduction blocks without causing electrochemical damage. However, HFAC produces a short initial response within the nerve, which can take seconds to disappear and stop. The initial reaction cannot be eliminated only by changing the HFAC waveform or electrode design. It is possible to completely neutralize the initial reaction by applying a short DC waveform to the adjacent electrodes, but if the DC waveform is applied many times, nerve conduction is impaired. Conduction damage can be due to the production of damaging electrochemical reaction products caused by DC waveforms at the required charge levels injected to block conduction in nerves.

Further, a DC waveform can be used as an alternative to the HFAC block. In fact, the DC waveform can be designed to eliminate adverse initial reactions or anodic cutoff excitations. However, these DC waveforms cause electrochemical damage to nerves. For example, damage can be caused by the formation of damaging electrochemical reaction products (eg, radicals), where the damaging electrochemical reaction products can occur when the interface charge injection capacity is exhausted. The charge injection capacity (or "charge capacity") is usually away from the electrode-electrolyte interface voltage (the voltage between the specific production of molecular oxygen and molecular hydrogen in a cyclic voltammogram (CV)) water windows. Previously refers to the amount of charge that the electrode can transmit.

The present disclosure relates to an electrical nerve conduction block (ENCB) as a whole, and more specifically to a method of treating a neuropathy with ENCB without producing a damaging electrochemical reaction product. For example, ENCB can be transmitted to nerves using a therapeutic transmission device (eg, electrodes) with electrode contacts, which are required for the desired nerve block if no irreversible electrochemical reaction occurs. Includes charged high charge capacitance materials (eg, made from and coated with the above high charge capacitance materials). Examples of high charge capacitance materials include platinum black, iridium oxide, titanium nitride, tantalum, poly (ethylenedioxythiophene) and the like.

Aspects of the present disclosure include methods for reducing pain in a subject. The method involves arranging electrode contacts to electrically communicate with nerves that carry pain-related signals. The method comprises applying ENCB to the nerve through electrode contacts without causing electrochemical damage to the nerve. The electrode contacts can include a high charge capacitance material, which prevents the formation of charge-damaged electrochemical reaction products transmitted by the ENCB. The method further comprises blocking the transmission of pain-related signals via nerves in the ENCB to relieve pain.

Another aspect of the disclosure includes a method of reducing muscle spasms in a subject. The method involves arranging electrode contacts to electrically communicate with nerves that carry signals associated with muscle spasms. The method further comprises applying ENCB to the nerve through electrode contacts without causing electrochemical damage to the nerve. The electrode contacts can include a high charge capacitance material, which prevents the formation of charge-damaged electrochemical reaction products transmitted by the ENCB. The method further comprises blocking the signal transmission through nerves at ENCB to stop muscle spasms.

Another aspect of the disclosure includes methods for treating neuropathy in a subject (eg, hyperhidrosis, dizziness, salivation, etc.). The method involves arranging electrodes so that they communicate electrically with nerves that carry signals associated with the disorder. The method further comprises applying ENCB to the nerve through electrode contacts without causing electrochemical damage to the nerve. The electrode contacts can include a high charge capacitance material, which prevents the formation of charge-damaged electrochemical reaction products transmitted by the ENCB. The method further comprises blocking the signal transmission through nerves in the ENCB to treat the disorder.

Another aspect of the disclosure includes a system with a waveform generator, controller and electrical contacts. The waveform generator is for generating an electrical nerve conduction block (ENCB). The controller is connected to a waveform generator. The controller is configured to receive an input containing at least one parameter to tune the ENCB. The electrical contacts are connected to the waveform generator. The electrical contacts are arranged so that they are in contact with the nerve. Electrical contacts include high charge capacitance materials that prevent the formation of charge-damaged electrochemical products transmitted on the ENCB. The electrical contacts are arranged to transmit the ENCB to the nerve and block the transmission of pain-related signals through the nerve.

The above and other features of the present disclosure will become apparent to those skilled in the art relating to the present disclosure when reading the following description with reference to the drawings. In the drawing
FIG. 5 illustrates an exemplary system capable of transmitting an electroneuronal conduction block (ENCB) to a nerve without causing electrochemical damage. , It is a figure which shows the example which a different treatment transmission apparatus is used by the system shown in FIG. It is a figure which shows the exemplary system of the waveform generator shown in FIG. 1 according to the input. FIG. 5 is a process flow diagram illustrating an exemplary method of transmitting ENCB to nerves without causing electrochemical damage. It is a process flow showing an exemplary method of adjusting the degree of ENCB applied to a nerve. It is a cyclic voltammogram showing several platinum black electrode contacts having different Q values. It is a figure which shows one example of the system which blocks the transmission of a nerve signal using DC ENCB without damaging a nerve. FIG. 5 illustrates an explanatory DC block test showing blocking spasms caused by proximal stimulation during the trapezoidal blocking phase. It is a figure explaining the vitality of the sciatic nerve conduction after DC ENCB. It is a figure which shows the example of the polyphase DC ENCB waveform. It is a figure which shows the experimental apparatus which uses DC plus HFAC non-onset blocking waveform, and ENCB. It is a figure which shows the DC transmission of a precharge pulse, a blocking phase of reverse polarity and a final charge phase. It is shown that DC blocks of different widths block different percentages of HFAC initial responses, and that the electrical nerve conduction block waveform affects the strength of the induced gastric muscles. , FIG. 5 shows the use of different gradients and multiple transformations in the DC waveform to avoid activating muscles when the current level changes, respectively. It is a figure which shows the DC block which cannot block the whole HFAC initial reaction because it is too short. FIG. 6 is a schematic showing a non-limiting example of potential clinical application of ENCB.

I. Definitions Unless otherwise limited, all technical terms used herein have the same meaning as commonly understood by those skilled in the art to which this disclosure belongs.

In the context of the present disclosure, the singular forms "1" and "above" may include the plural, unless otherwise explicitly indicated in the context.

As used herein, the term "contains" can identify the presence of a feature, step, operation, element and / or component to describe, but one or more other functions, steps, operations, Does not exclude elements, components, and / or combinations.

As described herein, the term "and / or" may include any and all combinations of one or more related listed items.

Further, although the terms "first", "second" and the like are used here to describe different elements, these elements are not limited to these terms. These terms are used only to distinguish one element from another. Therefore, the "first" element described below may be referred to as a "second" element if it does not deviate from the teachings of the present disclosure. Unless otherwise specified, the order of operations (or actions / steps) is not limited to the order shown in the claims or drawings.

As used herein, the terms "nerve block," "nerve conduction block," and "block" may be used interchangeably to refer to a pulse transmission failure at a point along a nerve. .. In some cases, nerve conduction can be blocked by extinguishing action potentials at some point as it travels along the nerve. In some other cases, nerve conduction is blocked by increasing the activation threshold of the target nerve and / or slowing the nerve conduction velocity, which is an incomplete block or parenchyma of nerve conduction. It leads to a target block.

As used herein, action potentials are "blocked" in nerve conduction when nerve transmission is completely extinguished (eg, 100% extinct).

As used herein, nerve conduction is "substantially blocked" when "incomplete nerve block" or "substantial nerve block" occurs. The terms "incomplete nerve block" and "substantial nerve block" can refer to partial blocks, of which less than 100% (eg, less than about 90%, less than about 80%, less than about 70%). , About 60% or less than 50%) of nerve-driven action potentials disappear.

As used herein, the term "electric nerve conduction block" or "ENCB" may refer to an external electrical signal (or waveform) capable of generating an electric field sufficient to block conduction in a nerve. can. The ENCB can include direct current (DC) waveforms (charge balanced biphasic, substantially charge balanced biphasic, or monophasic) and / or radio frequency alternating current (HFAC) waveforms.

As used herein, the term "DC waveform" can refer to the waveform of a current pulse of either polarity (eg, cathode or anode). In some cases, DC can be used as the first phase of the two-phase waveform. The second phase of the two-phase waveform reverses 100% of the total charge transmitted by the first phase (as a charge-balanced two-phase waveform) or less than 100% of the total charge transmitted by the first phase. This reduces the production of damaging reaction products that can damage the electrodes for transmitting nerves and / or DC. In some other cases, DC can be applied as a single-phase waveform.

As used herein, the term "high frequency" (eg, HFAC) for alternating current can refer to frequencies above about 1000 hertz (kHz), such as about 5 kHz to about 50 kHz.

As used herein, the term "electrical communication" refers to the ability of an electric field to transfer to a nerve and have a neuromodulatory effect (eg, blocking the transmission of nerve signals) within the patient's nerves. be able to.

As used herein, if signal transmission (or action potential conduction) is blocked, then an "electrical signal" (eg, a controlled voltage or controlled current) becomes a nerve (or nerve group). ) Can be applied to axons, cell bodies or dendritic processes) and does not damage nerve tissue.

As used herein, when related to nerves, the term "signal transmission" can refer to the conduction of action potentials within nerves.

As used herein, the term "therapeutic transmission device" can refer to a device that is arranged to transmit ENCB to a nerve. In some embodiments, the therapeutic transmission device may include an electrode having one or more contacts. The one or more contacts may be made of a high charge capacitance material, which is an ion device (in an electrolyte, for example, interstitial fluid) via electrons in a metal (conductor / lead wire). Provides current conversion to). In some cases, the electrodes contribute to shaping the electric field generated by the contacts. As an example, the electrodes can be implanted and / or positioned on the patient's skin surface.

As used herein, the term "high charge capacitance material" refers to a material that carries the charge required for the electrode contacts to block conduction in less nerves and parts without damaging the nerves. Can be pointed to.

As used herein, the term "Q factor" is the value of the total amount of charge that can be transmitted by an electrode contact before it triggers an irreversible electrochemical reaction that can trigger the formation of damaging reaction products. Can be pointed to. For example, a high charge capacitance material can have a large Q value, which allows a larger charge to be transmitted to the electrode contacts before causing an irreversible electrochemical reaction.

As used herein, the term "damaging reaction product" can refer to a reaction that damages a nerve, another part of the body in close proximity to an electrode contact and / or an electrode contact. For example, the damaging reaction product can be due to oxygen precipitation or hydrogen precipitation. As another example, the damaging reaction product can result from the dissolution of the material at the electrode contacts. As used herein, ENCBs are considered "safe" if blocking occurs without producing damaging reaction products.

As used herein, the term "electrode / electrolyte interface" can refer to a two-layer interface, where the electrode and electrolyte (eg, the region of the patient's body, eg, between). A potential difference is established with the plyte.

As used herein, the term "geometric surface area" of an electrode contact is obtained by multiplying the length by the length of the two-dimensional surface area of the electrode contact, eg, the two-dimensional outer surface area of the electrode contact. It can refer to the surface area of the smooth surface on one side of the electrode contacts.

As used herein, the terms "effective surface area" and "true surface area" of an electrode contact refer to the surface area estimated from the area within the curve of the cyclic voltammogram ("CV") of the electrode contact. Can be done.

As used herein, the term "waveform generator" can generate electrical waveforms (eg, charge-balanced biphasic DC, substantially charge-balanced biphasic DC, single-phase DC, HFAC, etc.). Device can be pointed to, where the electrical waveform can be provided to the electrode contacts to provide ENCB. The waveform generator can be implanted, for example, inside the patient and / or outside the patient.

As used herein, the term "nerve system" refers to a network of nerve cells and nervous tissue that transmits electrical pulses (also called action potentials) between parts of the patient's body. Neural systems can include peripheral and central nervous systems. The peripheral nervous system includes motor nerves, sensory nerves and autonomic nerves, and interneurons. The central nervous system includes the brain and spinal cord. As used herein, the terms "nerve" and "nervous tissue" are compatible to refer to tissues of the peripheral or central nervous system, unless specifically stated to refer to one and exclude the other. Can be used for.

As used herein, the terms "disorder" and "neuropathy" are interchangeably used to refer to a disease or disorder characterized by abnormal conduction in at least one or more nerves. Can be used. In some cases, abnormal conduction may be associated with pain and / or seizures. Examples of neuropathy include stroke, brain injury, spinal cord injury (SCI), cerebral palsy (CP) and multiple sclerosis (MS), and cancer, joint replacement, endometriosis, hyperhidrosis, dizziness, saliva. It can include secretions, torticollis, neurological tumors, saliva, etc.

As used herein, the terms "patient" and "subject" can be used interchangeably to refer to any warm-blooded organism suffering from a neuropathy. Examples of warm-blooded organisms can include, but are not limited to, humans, pigs, rats, mice, dogs, cats, goats, sheep, horses, monkeys, monkeys, rabbits, cows and the like.

II. Overview The entire disclosure relates to the Electrical Nerve Conduction Block (ENCB). ENCB also refers to signal transmission (also referred to as "conduction" of action potentials) in one or more nerves to prevent unwanted neural activity of neuropathy such as pain, muscle spasticity, hyperhidrosis, dizziness, salivation. Can be blocked). However, traditionally, ENCB has not been used to treat unwanted neural activity in such neurological disorders. One of the reasons for disagreeing with the use of ENCB is the occurrence of unwanted side effects, such as the production of dangerous electrochemical reaction products. The high charge capacitance electrode contacts of the present disclosure can substantially eliminate such electrochemical damage to the charge used in the ENCB. Accordingly, the present disclosure relates to methods of treating neuropathy with ENCB without causing electrochemical damage to nerves, the patient's body or electrodes.

A therapeutic transmission device (eg, an electrode) with electrode contacts containing a high charge capacitance material can be used to transmit ENCB to the nerve. Using a high charge capacitance material, the electrode contacts of the present disclosure can transmit ENCB in the absence of the initial reaction characteristics of the HFAC waveform and no electrochemical damage due to the application of the DC waveform. Generally, the high charge capacitance electrode can have a Q value of about 100 μC or more. In other words, the high charge capacitance electrode can transmit a charge of about 100 μC or more without producing an irreversible reaction product. However, in some cases, the high charge capacitance electrode can have a Q value between about 1 μC and about 100 μC. In some other cases, the high charge capacitance electrode can have a Q value on the order of about 10 μC.

Compared to conventional stimulation electrodes made of, for example, platinum or stainless steel, high charge capacitance materials can be used to safely transmit more charge over longer periods of time. In some cases, the high charge capacitance material can have ^{a charge injection capacitance of about 1 to about 5 mC / cm 2} (charge density that can be safely transmitted by the material). In comparison, the polished platinum (non-high charge capacity material) has a charge injection capacity of ^{about 0.05 mC / cm 2.} For electrode contacts containing high charge capacitance materials, the effective surface area of the electrode contacts increases by several orders of magnitude relative to the geometric surface area. Thus, as an example, DC can be transmitted over 10 seconds by unipolar nerve cuff electrode contacts without any nerve damage. Therefore, the present disclosure provides an excellent block that is effective, reversible, and "does not develop".

III. System In some aspects, the present disclosure relates to a system 10 (FIG. 1) that treats a neuropathy by blocking signal transmission through a small portion of the target nerve associated with the neuropathy. The system 10 can apply an electrical nerve conduction block (ENCB) to the nerve to block signal transmission in the nerve. Advantageously, ENCBs can be transmitted at the required charge level without causing the formation of electrochemical reaction products that cause electrochemical damage. For example, ENCB can be used for motor nerve block, sensory nerve block, autonomic nerve block, central nervous system block, interneuron block and the like. Contrary to other types of blocks (eg, neurolies), nerves restore normal conduction when ENCB is no longer applied.

The system 10 may include a waveform generator 12, which is connected to a treatment transmission device 14 that includes one or more electrode contacts 16 (eg, by wire or wireless connection) and treatment. It communicates electrically with the transmission device 14. The waveform generator 12 can generate an electrical waveform (also referred to as an "ENCB waveform" or abbreviated as "ENCB") that blocks the signal from being transmitted through nerves. In some cases, the electrical waveform may be a single-phase direct current (DC) waveform, a charge-balanced two-phase DC waveform and / or a substantially charge-balanced two-phase DC waveform. In some other cases, the waveform may be a radio frequency alternating current (HFAC) waveform.

The therapeutic transmission device 14 receives the generated electrical waveform and directs the ENCB to a nerve (also referred to as a "target nerve" or "nervous tissue") by one or more electrode contacts 16 (unipolar and / or bipolar). To transmit. For example, the waveform generator 12 can generate different waveforms to apply waveforms at different times and / or with different electrode contacts. For example, the waveform generator 12 generates DC and HFAC waveforms that are applied at different times. As another example, the waveform generator 12 can generate multiple DC waveforms applied by different electrode contacts 16 with different time series characteristics.

Since at least one or more electrode contacts 16 can include a high charge capacitance material, the therapeutic transmission device 14 can transmit the ENCB without forming an irreversible, damaging electrochemical reaction product. Generally, a high charge capacitance material is any material in which the electrode contacts 16 are irreversible, do not form damaging reaction products, and can supply the charge required to transmit the desired nerve conduction block. May be good. For example, the water window of the high charge capacitance material can be widened so that the required charge can be transmitted to the block without the precipitation of hydrogen or the precipitation of oxygen. Non-limiting examples of high charge capacitance materials include platinum black, iridium oxide, titanium nitride, tantalum, poly (ethylenedioxythiophene) and suitable combinations.

In some examples, the one or more electrode contacts 16 can be made from a high charge capacitance material. In another example, the one or more electrode contacts 16 may include a conductive material (eg, platinum, stainless steel, etc.) that is at least partially coated with a high charge capacitance material. In another example, the one or more electrode contacts 16 may include electrode contacts made from a high charge capacitance material and at least partially coated with the high charge capacitance material. In yet another example, the one or more electrode contacts 16 may include a contact that includes a high charge capacitance material and another contact that does not contain a high charge capacitance material.

In one example, one or more electrode contacts 16 can have a geometric surface area of ^{about 1 mm 2.} In another example, the geometric surface area of one or more electrode contacts 16 is about 3 mm ² to about 9 mm ² . In some examples, each of the one or more electrode contacts 16 can have approximately equal geometric surface areas. In another example, the one or more electrode contacts 16 can have different geometric surface areas.

In some cases, the treatment transmission device 14 may be an electrode. In some non-limiting examples, the treatment transmission device 14 is an electrode having a plurality of continuous electrode contacts 16 (eg, a nerve cuff electrode shown in FIG. 2 or a planar interface nerve electrode (FINE) shown in FIG. 3). There may be. However, the therapeutic transmission device 14 may have other configurations not shown, such as spiral cuff electrodes or other nerve cuff electrodes, meshes, straight rod-shaped leads, paddle-shaped leads, multi-display contact electrodes or penetrating nerves. It can have a disc-type contact electrode including an electrode.

FIG. 4 shows an exemplary system 40 that controls the parameters of the electrical waveform generated by the waveform generator 12. The system 40 may include a controller 42, which receives an input (including at least one parameter) to the waveform generator 12 so that the electrical waveform can be transmitted to the adjustment and / or treatment transmission device 14. The signal can be transmitted, which allows the appropriate ENCB to be transmitted to the nerve. For example, based on the input, the controller 42 can specify timing parameters, intensity parameters, waveform parameters, and / or whether to transmit ENCB to any of one or more electrode contacts 16. .. In one example, the controller 42 can specify an intensity parameter to block part of the signal transmission through the nerve ("adjusting the degree of blocking". By blocking only part of the signal transmission. , The negative consequences of signal transmission can be reduced or eliminated, along with the transmission of signals through other parts of the nerve (eg, allowing spontaneous movement of muscles and blocking muscle spasms). To enable.

In some cases, the controller 42 may be part of an open-loop control system, where the input is a patient or medical professional user input, which is "safe" pre-limited by the medical professional. Can be limited by the "na" parameter). For example, it can be input via an analog device (eg, switch, dial, etc.), which allows the user to input an analog value. As another example, input can be made via a digital device (eg, keyboard, microphone, etc.), which allows the user to input a numeric value. The controller 42 can analyze the input and transmit a signal containing parameters adjusted based on the input to the waveform generator 12.

In other cases, the controller 42 may be part of a closed-loop control system, which can receive input from entities other than the user. For example, a closed-loop control system can use one or more sensors capable of sensing changes in physiological parameters. Inputs can be based on detected changes. The controller 42 can analyze the inputs and transmit to the waveform generator 12 a signal containing parameters adjusted based on the inputs.

IV. Methods Another form of the disclosure includes methods for treating neuropathy by using a nerve conduction block (ENCB) to block signal transmission through at least some of the nerves associated with the neuropathy. be able to. ENCB can be applied by a single-phase direct current (DC) waveform, a parallel-charge two-phase DC waveform and / or a substantially equilibrium charge two-phase DC waveform. As another example, the ENCB can include a radio frequency alternating current (HFAC) waveform. Advantageously, ENCB can be applied without causing negative side effects, eg, electrochemical damage at the charge injection level required for ENCB.

FIG. 5 shows an example of a method 50 of transmitting ENCB to nerves without causing electrochemical damage. FIG. 6 shows an example of a method 60 for adjusting the degree of ENCB applied to a nerve. For example, the methods 50 and 60 can be applied by using the systems shown in FIGS. 1 and 4. A flowchart described as a flow chart is shown in the method 50 and the method 60 of FIGS. 5 and 6. For brevity, methods 50 and 60 are shown as being performed continuously. However, it is understood and understood that the present disclosure is not limited by the order shown and that some steps can be performed in a different order and / or at the same time as the other steps shown and described herein. I want to be recognized. Also, not all forms shown are required to carry out method 50 and method 60.

With reference to FIG. 5, an example of a method 50 of transmitting ENCB to nerves without causing electrochemical damage is shown. In 52, the electrode contacts of the treatment transmission device (eg, one or more electrode contacts 16 of the treatment transmission device 14) are arranged to electrically communicate with a nerve transmitting a signal related to neuropathy. Can be done. At least one electrode contact can include a high charge capacitance material (eg, composed of and coated with a high charge capacitance material). The high charge capacitance material allows the electrode contacts to transfer the required charge to the conduction block without forming irreversible and damaging reaction products. For example, a high charge capacitance material allows an electrode to transmit at least 100 μC before an irreversible electrochemical reaction occurs in the material. However, in some cases, the high charge capacitance electrode can have a Q value of about 1 μC to about 100 μC. In other cases, the high charge capacitance electrode can have a Q value on the order of about 10 μC. Non-limiting examples of high charge capacitance materials include platinum black, iridium oxide, titanium nitride, tantalum, poly (ethylenedioxythiophene) and suitable combinations.

At 54, ENCB can be applied by at least one contact without causing electrochemical damage to the nerve. In other words, high charge capacitance materials carry the charge required for one or more contacts to block conduction in the nerve without causing irreversible electrochemical reactions and damaging reaction products. Is possible. At 56, the neuropathy can be treated by blocking the transmission of signals associated with the neuropathy (eg, action potential conduction). Since the ENCB is reversible, when the transmission of the ENCB is stopped, the normal signal transmission via the nerve is restored.

With reference to FIG. 6, an example of method 60 for adjusting the degree of ENCB applied to the nerve is shown. At 62, to block the transmission of signals related to neuropathy (eg, action potential conduction) through the nerve, ENCB (eg, generated by the waveform generator 12 at the first level with the first parameter). Can be applied to nerves (eg, via a therapeutic transmission device 14). At 64, an input (eg, an input up to the controller 42) can be received. Inputs may come from users (eg, patients, medical professionals, etc.) or from automatic (eg, from one or more sensors that detect one or more physiological parameters). ) May be. In other words, method 60 can operate as open loop control and / or closed loop control. At 66, the ENCB (eg, one or more ENCB-like parameters) can be adjusted to block the transmission of some signals. In other words, ENCB can be adjusted to block only some of the action potentials through nerves (or groups of nerves) from being conducted and some other action potentials to be conducted through nerves.

V. Example-Electrode Configuration and Waveform Design The following examples show the configuration of high charge capacitance electrode contacts and the design of various waveforms transmitted by the electrode contacts without causing nerve damage. By transmitting the desired electric field through the tissue to the desired neural configuration, the electrode contacts can transmit ENCB to any nerve, including peripheral and / or central nervous system configurations. The specific waveform description is an example, and the waveform actually used for ENCB is a DC electric waveform (for example, equilibrium charge biphasic, substantially equilibrium charge biphasic, or monophasic) and / or high-frequency alternating current. (HFAC) waveforms can be included.

High Charge Capability Electrode Contact In this example, the electrode contact is made from a high charge capacitance (“HiQ”) material to achieve ENCB without causing electrochemical damage to the nerve. The Hi-Q material significantly increases the charge injection capacity of the electrode contacts, where the charge injection capacity is quantified by the Q value. The Q value is defined as the amount of charge that the electrode contacts can transmit before an irreversible electrochemical reaction occurs in the material, or before an irreversible chemical reaction occurs because of the material. An example of the Hi-Q material used in this experiment is a platinum piece (also referred to as platinum black). This indicates that platinum pieces can transmit DC nerve blocks to nerves without causing electrochemical damage to the nerves, even after repeated application multiple times (eg> 100 times).

The platinum single electrode contacts are configured as follows. The unipolar nerve cuff electrode contact is made of platinum foil. Then, these electrode contacts are plated with platinum in a chloroplatinic acid solution to produce a platinum black coating layer having various roughness coefficients over 50-600. Cyclic voltamogram used for different platinum black electrode contacts at _{0.1 M H 2} SO ₄ (shown in FIG. 7) to identify the amount of charge that can be safely transmitted to a platinum piece by identifying the water window. To generate.

By calculating the charge associated with hydrogen adsorption with respect to the standard Ag / AgCl electrode contact from -0.25V to + 0.1V, the amount of charge (Q value) that can be safely transmitted by the platinum single electrode contact is estimated. The typical Q value range of these platinum single electrode contacts is 2.9 mC to 5.6 mC. On the other hand, the Q value of the standard platinum foil electrode contact is 0.035 mC.

Acute experiments were performed in Sprague-Dawley rats to test the effectiveness of the DC nerve block of the platinum single electrode contact and the control platinum electrode contact. Under anesthesia, the sciatic nerve and the intestinal muscle on one side were dissected. Bipolar stimulation electrode contacts were located proximal and distal to the sciatic nerve. Proximal stimulation (PS) causes muscle spasms and allows quantification of motor nerve blocks. Distal stimulation also caused muscle spasms, which were compared to PS-induced muscle spasms as a measure of nerve damage at DC unipolar electrode contacts. As shown in FIG. 8, the unipolar electrode contact is arranged between the two stimulation electrode contacts.

DC waveforms were created using current controlled waveform generators (Keithley Instruments, Solon, Ohio). As shown in FIG. 9 (B) below, the waveform is biphasic and includes a trapezoidal blocking phase followed by a square charged phase. Ramp up and down ensure that there is no DC initial discharge. The DC parameters were selected so that the total charge to be transmitted was smaller than the Q value for the given electrode contacts. Then, following each cathode (blocking) pulse is the charging phase. In the charging phase, 100% charge is returned to the electrode contacts by the anodic pulse maintained at 100 μA.

The platinum single electrode contacts provide a conduction block and also keep the total charge below the maximum Q value for each electrode contact. FIG. 9 shows a test to obtain a complete motor block using a DC waveform with a peak width of 0.55 mA. As shown in FIG. 9 (A) above, PS-induced muscle spasms were completely blocked during the plateau phase of DC transmission.

FIG. 10 shows the effect of the cumulative DC dose of the five platinum single electrode contacts compared to the standard platinum electrode contacts. As shown in FIG. 9, the DCs were transmitted (subplot below). Each DC cycle was followed by PS and DS, producing some convulsions (not shown in FIG. 10). The PS / DS ratio is a measure of acute nerve damage. This ratio should approach 1 if the nerve normally conducts through the region below the block electrode contacts. The platinum electrode contacts showed nerve damage less than 1 minute after transmission of 50 mC, and nerves did not recover within the following 30 minutes. Platinum single electrode contacts show no significant signs of nerve damage within the duration of each experiment with cumulative charge transfer up to 350 mC. Repeated experiments using other platinum single electrode contacts with variable Q values gave similar results.

Polyphase DC waveform ENCB
In one example, the ENCB waveform contains a polyphase DC. As shown in FIG. 11, the polyphase DC includes a cathode DC phase and a mutual anode DC phase, and the cathode DC phase and the mutual anode DC phase circulate continuously between four consecutive unipolar electrode contacts. By doing so, there is no nerve damage and there is a continuous nerve block. In some cases, the polyphase DC may be charge-balanced or substantially charge-balanced, thereby inverting the current drive and performing charge equilibrium with respect to the Helmholtz bilayer (HDL). , Obtains the accumulated charge after the blocking time.

It should be understood that the cathode DC does not need to be applied first. Thus, polyphasic DCs can be applied to nervous tissue, including applying anodic DC currents and applying mutual cathodic DC currents. One phase of DC is configured to produce a complete, substantially complete, or partial nerve block, and the other phase is therapeutic transmission (eg, by reversing the current). It is configured to reduce or balance the charge returning to the device. An exemplary polyphasic DC includes a relatively slow current lamp that is unable to produce an initial response in nervous tissue.

For example, with reference to FIG. 11, a nearly trapezoidal polymorphic DC waveform transmitted by the four electrode contacts (“1”, “2”, “3” and “4”) of the treatment transmission device is shown. .. Each cathode and anode DC phase begins with a lamp and ends with a lamp, which prevents or substantially prevents any axonal discharge. For example, in the cathode DC plateau, there is a complete nerve block. As mentioned above, the cathodic DC phase causes a nerve block, which is followed by a current reversal (anodic DC phase) to balance the charges transmitted by the therapeutic transmission device. The anode charging time can be approximately equal to or reasonably longer than the cathode block time. The cycle of cathode block and anode charging can be sequentially applied to nerve tissue without any nerve damage. Similarly, the order of the DC phases can be reversed, the anodic DC phase can cause nerve blocks, and the cathodic DC phase can balance the charges transmitted by the therapeutic transmission device.

In some cases, the cathode DC phase is done as follows. The DC having the first DC width can be applied to the nerve tissue. Then, the first DC increases to the second DC width within the first time zone. DCs with a first width are insufficient to produce partial or complete nerve blocks. The second DC width is then largely maintained within a second time period sufficient to generate a complete nerve block. After the second time zone, the second DC width is reduced to a third DC width equal to or approximately equal to the first DC width.

In some examples, the total net charge transmitted by any of the electrode contacts can be equal to or nearly equal to zero. Advantageously, transmitting a net zero charge is fairly safe for nervous tissue. However, since the entire charge cannot be transmitted by the first phase due to an external factor, the waveform does not need to be in perfect charge equilibrium, and needs to be substantially only in charge equilibrium.

Application of DC and HFAC In another example, the ENCB has a DC and HFAC waveform to reduce or eliminate the "initial reaction" (caused by HFAC) without causing electrochemical damage (caused by DC). Combinations of transmissions can be included. HFAC has been demonstrated to provide a safe, local, reversible electrical nerve conduction block. However, at the onset of HFAC, HFAC causes a short but violent initial reaction. During the early phase of the HFAC, blocking nerve conduction with short-duration DCs can solve the problem of onset, but DCs can generate nerve blocks and within a short time period. Causes nerve tissue damage. By using the HiQ DC electrode contacts, the damage caused by the damaging electrochemical reaction products caused by DC can be reduced or eliminated.

As shown in FIGS. 12A-C, a successful non-initial block was demonstrated using a combination of Hi-QDC electrode contacts and HFAC electrode contacts. FIG. 12A shows an example of an experimental device that can be used to apply DC and HFAC to nerves. As shown in FIG. 12C, applying only HFAC leads to an initial reaction. However, when DC was applied before HFAC, this block was realized without an initial reaction, as shown in FIG. 12B. Experiments performed in this way achieved more than 50 continuous block sections without degrading nerve conduction. The DC block (2.4 mA) was repeatedly applied over about 2 hours, the cumulative DC transmission was 1500 seconds, and there was no decrease in nerve conduction. FIG. 12B (compared to FIG. 12C) shows that the combination of HFAC and Hi-Q DC nerve block is used to successfully eliminate the initial response.

An example of a combined HFAC and Hi-Q DC nerve block allows DC to be transmitted in a time zone sufficient to block the entire initial response of HFAC. This usually lasts from 1 to 10 seconds, so DC should be transmitted throughout the time zone. As shown in FIG. 13, a way to further extend the total plateau time for DC to be safely transmitted is to use a "precharge" pulse. The precharge pulse involves transmitting a DC wave of opposite polarity from the desired blocking effect within a certain amount of time up to the maximum charge capacitance of the electrode contacts. Then, the DC polarity is inverted to produce a blocking effect. However, because the electrode contacts are "pre-charged" to the opposite polarity, the block can be transmitted for a longer period of time (eg, twice as long). At the end of the extended blocking phase, the polarity is reversed again to the same polarity as the precharged phase, reducing the total charge by transmitting this final phase. In most cases, the total net charge of this waveform will be zero, but a beneficial effect can be achieved even if the total net charge is not in perfect equilibrium.

As shown in FIGS. 14A-B, changing the level of DC can partially or completely block the initial reaction from HFAC. FIG. 14A is a diagram showing a large initial response by applying HFAC alone before muscle activity is suppressed. FIG. 14B is a graph showing that the sloping DC waveform reduces PS-induced ballismus and minimizes the initial response evoked by the HFAC waveform. The bar under "HFAC" indicates when it was turned on. The bar under "DC" is where DC tilts from zero down to the blocking level and then back to zero (zero DC is not shown). Even in the case of prominent nerve blocks, it is also useful to assess nerve health by verifying small responses. The depth of the DC block can be evaluated in this way.

Multi-gradient conversion can help avoid initial reactions, especially in real-world devices, where the DC current width changes discretely over time (gradient). This is shown in FIGS. 15 and 16, which show the results of the rat sciatic nerve. In these examples, the DC starts with a low gradient to prevent nerve discharge at low amplitude. The gradient can then be increased to reach the blocking amplitude faster. When the DC block amplitude is reached, the block lasts for the duration required to block the HFAC initial reaction. When the DC reaches the blocking plateau, the HFAC is turned on. HFAC is turned on depending on the amplitude required to block. When the initial response is complete, DC decreases first quickly and then slowly to prevent nerve activation. The DC then slowly transitions to the charging phase, where the total charge injection is reduced. In this example, the charging phase is low amplitude and lasts for 100 seconds or longer. The HFAC block can be maintained throughout this time, and if the nerve block is still needed, it can continue after the DC transmission is complete. When the entire period of the desired block is complete (which can take several hours in some cases), the HFAC can be turned off to restore the nerve to normal conduction. This process can be repeated as many times as needed to produce nerve blocks on demand to treat the disease.

FIG. 17 shows maintaining DC within the duration of the entire initial reaction from HFAC to block the entire initial reaction. In this example (rat sciatic nerve), the initial response lasted about 30 seconds. The DC waveform (blue trace) initially blocks the initial reaction, but as the DC tilts back to zero, the initial reaction becomes apparent (in ~ 50 seconds). It shows a very long DC block waveform and combines HFAC and DC blocks to achieve a block that does not develop.

VI, eg-potential clinical applications The electrodes and waveform designs described above can be used in many different clinical applications, without producing damaging electrochemical reaction products, ENCB (any peripheral or central nervous system). Also applied to system structure) to treat neuropathy. Since ENCBs can be reversible, conduction in stimulated nerves can be restored when ENCBs are turned off.

ENCB can be used to treat a large number of different neuropathy in patients. For example, in FIG. 18, different types of ENCBs are applied to different nerves in different ways, including torticollis (eg, open-loop control), neuroma pain (open-loop control), cramps (eg, closed-loop control) and spasticity. It has been shown that conditions / joint contractures (eg, open-loop or closed-loop control) can be treated. Other uses of ENCB include the treatment of pain (eg, cancerous pain, back pain, joint replacement pain, endometriotic pain and other types of pain), hyperhidrosis, dizziness and salivation. .. Still other uses of ENCB include relief of the urethral sphincter and relief of refractory hiccups. As mentioned above, each treatment of these neuropathy has no negative side effects and uses electrode contacts containing high charge capacitance material (eg, electrode contacts of cuff electrodes placed next to the nerve, Alternatively, one or more waveforms (DC and / or HFAC) can be applied by means of the electrode contacts of the external electrodes). In some cases, ENCBs can be combined with other types of nerve blocks, such as pharmacological or heat blocks (including nerve overheating or cooling) to facilitate treatment of these nerve disorders. ..

Spasms To prevent or reverse joint contractures, ENCBs can be used to reduce or eliminate muscle spasms or spasms. It is particularly applicable to cerebral palsy, stroke and multiple sclerosis, and spinal cord injury and post-orthopedic disease. In each of these cases, muscle spasms and spasms are serious complications that cause the joints to contract and continue to contract when the patient wants to relax. Over time, such contractions result in physiological shortening of the contracted muscles, causing permanent joint contractures and damage to the range of motion of the joints. When these contractures occur, traditional treatments are usually damaging and irreversible and generally ineffective. For example, traditional treatment methods include chemically or surgically damaging nerve fibers or surgical removal of tendons.

In contrast, ENCB can advantageously be applied to block spasmodic signals on motor or sensory nerves and relax muscles. In some cases, an open-loop control system can be used to apply ENCB, where the patient is given a switch or other input device to turn the block on and off and control the degree of block.

ENCB is reversible and the patient can relax the muscles as needed and reverse the block as needed. For example, ENCB can be used during night breaks or when the individual has little movement to completely relax the muscles, but can be stopped (reversed) when the individual is moving. Treatment with ENCB is harmless and can be treated early during the course of the disease, preventing the development of contractures.

In some cases, ENCB can be used to generate partial nerve blocks, which is beneficial in maintaining motor function. In partial blocking, nerve signals that are part of the muscle fibers and not all are blocked and muscle contraction strength is reduced. This can allow the spasmodic muscles to move spontaneously without causing the intense contractions commonly found in the spasmodic muscles. In this case, the antagonist muscles may be strong enough so that the joints move within the entire range of motion.

One application of ENCB is to prevent / treat contractures in spastic cerebral palsy. In cerebral palsy, the spastic ankle sole flexors and adductor muscles provide a characteristic pattern of contracture, the limiting function of which makes personal hygiene difficult and painful. Because these operations are irreversible, tendon extension or release of esophageal tension by neurolies is usually done only as a last resort. In some cases, reversible ENCB is applied to the obturator nerve to relax the hip abductor muscle and to the posterior tibial nerve to block plantar flexion of the ankle joint. Will be done. ENCB can be applied over several hours throughout the day so that the block can be turned off when the patient needs exercise. Another application of ENCB is torticollis, which is an involuntary movement caused by diseases such as dystonia, chorea and spasms by blocking the sternocleidomastoid muscle and possibly the posterior cervical muscle. It can be used to treat / prevent exercise and convulsions.

ENCB can be realized by a plurality of methods. In some cases, charge-balanced or unbalanced HFAC waveforms (voltage or current control) can be used to generate rapidly induced and rapidly reversible neural conduction blocks. A typical waveform frequency can be between 5 and 50 kHz. The waveform may be continuous or interrupted, and each pulse can have a variety of shapes, including squares, triangles, sinusoids, and the like.

In other cases, a charge-balanced DC waveform that decreases the current to the opposite polarity, including increasing to a plateau of one polarity that can last for a period of time (eg, 10 seconds), can be used for ENCB. The plateau of each phase may be the same, but usually the second phase is 10-30% of the width of the first phase. Total charge transmission is zero or substantially less than the charge in each phase (eg, less than 10% charge imbalance). The waveform produces depolarized or hyperpolarized nerve blocks during the first phase plateau and, in some cases, also during the second phase plateau. The current is often increased from zero to a slow plateau within seconds to eliminate the generation of action potentials in the nerve. Further, by cycling between different contacts using a plurality of electrode contacts, a DC waveform can be transmitted to a nerve to maintain a constant conduction block.

In other cases, DC and HFAC waveforms can be combined to generate nerve blocks with the desired characteristics of each type of ENCB. A charge-balanced DC can first be established and used to block an initial reaction from HFAC that normally lasts several seconds. When the initial reaction is complete, the charge equilibrium DC waveform can be terminated (usually after charge equilibrium) and the block can be maintained with the HFAC waveform.

Pain ENCB can be used, for example, to treat acute and chronic pain due to cancer, pancreatitis, neuromas, endometriosis, post-herpetic neuralgia, back pain, headache and joint replacement. In fact, as an alternative to neurolies or chemical blocks, ENCB can be used to block any nerve conduction that leads to a pain sensation. Notably, ENCB is reversible and can be used early in treatment. This is because any side effects can be immediately mitigated by turning off the block. The strength and range of ENCB can be adjusted (eg, as an open loop system).

Depending on the pain treated with ENCB, the electrode contacts can be part of the cuff electrode, electrode contacts located near the target nerve, paddle-type electrodes, mesh-type electrodes, and the like. In some cases, instead of blocking the sensory nerves, ENCB can be transmitted to the autonomic nerves (eg, the sympathetic ganglia), which can cause the side effects of the dull squealing sensation felt by the stimulus.

ENCB can be realized by a plurality of methods. In some cases, charge-balanced or unbalanced HFAC waveforms (voltage or current control) can be used to generate rapidly induced and rapidly reversible neural conduction blocks. Typical waveform frequencies can be between 5 and 50 kHz. The waveform may be continuous or interrupted, and each pulse can have a variety of shapes, including squares, triangles, sinusoids, and the like.

In other cases, a charge-balanced DC waveform that decreases the current to the opposite polarity, including increasing to a plateau of one polarity that can last for a period of time (eg, 10 seconds), can be used for ENCB. The plateau of each phase may be the same, but usually the second phase is 10-30% of the width of the first phase. Total charge transmission is zero or substantially less than the charge in each phase (eg, less than 10% charge imbalance). The waveform produces depolarized or hyperpolarized nerve blocks during the first phase plateau and, in some cases, also during the second phase plateau. The current is often increased from zero to a slow plateau within seconds to eliminate the generation of action potentials in the nerve. Further, by cycling between different contacts using a plurality of electrode contacts, a DC waveform can be transmitted to a nerve to maintain a constant conduction block.

In other cases, DC and HFAC waveforms can be combined to generate nerve blocks with the desired characteristics of each type of ENCB. A charge-balanced DC can first be established and used to block an initial reaction from HFAC that normally lasts several seconds. When the initial reaction is complete, the charge equilibrium DC waveform can be terminated (usually after charge equilibrium) and the block can be maintained with the HFAC waveform.

Urethral sphincter relaxation Reversible ENCBs can be used to generate urethral sphincter relaxation in response to commands (eg, in an open-loop system). One important application example is the design of an electrical stimulation system that results in the bladder being drained empty for an individual with spinal cord injury. In these systems, stimulation of the sacral root causes the bladder to contract as it is expelled, but it also causes unwanted contraction of the sphincter. The methods of the present disclosure can be bilaterally applied to the pudendal nerve to prevent sphincter activity during bladder activation. After the bladder is empty, turn this block off and recover to self-control. Block electrode contacts can also be used as a stimulus to activate weak sphincters and improve self-control. Nerve conduction blocks on the sacral sensory root can also be used to improve self-control by preventing spontaneous bladder contractions. The method can also be used to control bladder sphincter incoordination in spinal cord injury.

Hyperhidrosis Reversible ENCB can be applied to the neural structure of the sympathetic nervous system (eg, in an open loop system) to treat hyperhidrosis (palm sweating). ENCB is a reversible alternative to traditional sympathectomy involving permanent surgical destruction or rupture of fibers in the sympathetic chain. Sympathectomy is permanent and may have irreversible side effects (eg, it does not excessively reduce dry skin and other side effects associated with the destruction of the sympathetic nervous system). In contrast, ENCB can produce similar ideal effects without causing permanent damage to any neural structure. ENCB can be applied and / or adjusted as needed to provide the desired degree of reduction in palm sweating without unwanted side effects.

In one example, ENCB can be applied to specific areas of the sympathetic nervous system. For example, the ENCB is placed near the target sympathetic ganglion to block or down-control the action potentials transmitted within or between the sympathetic ganglia so as to generate an electric field of sufficient strength. It can be applied by the electrode contact. In other cases, ENCB can be applied by nerve cuff electrodes located around the sympathetic nerve chain (eg, around the sympathetic nerve fibers between the ganglia, sympathetic roots or sympathetic ganglia).

ENCB can be realized by a plurality of methods. In some cases, charge-balanced or unbalanced HFAC waveforms (voltage or current control) can be used to generate rapidly induced and rapidly reversible neural conduction blocks. Typical waveform frequencies can be between 5 and 50 kHz. The waveform may be continuous or interrupted, and each pulse can have a variety of shapes, including squares, triangles, sinusoids, and the like.

In other cases, a charge-balanced DC waveform that decreases the current to the opposite polarity, including increasing to a plateau of one polarity that can last for a period of time (eg, 10 seconds), can be used for ENCB. The plateau of each phase may be the same, but usually the second phase is 10-30% of the width of the first phase. Total charge transmission is zero or substantially less than the charge in each phase (eg, less than 10% charge imbalance). The waveform produces depolarized or hyperpolarized nerve blocks during the first phase plateau and, in some cases, also during the second phase plateau. The current is often increased from zero to a slow plateau within seconds to eliminate the generation of action potentials in the nerve. Further, by cycling between different contacts using a plurality of electrode contacts, a DC waveform can be transmitted to a nerve to maintain a constant conduction block.

In other cases, DC and HFAC waveforms can be combined to generate nerve blocks with the desired characteristics of each type of ENCB. A charge-balanced DC can first be established and used to block an initial reaction from HFAC that normally lasts several seconds. When the initial reaction is complete, the charge equilibrium DC waveform can be terminated (usually after charge equilibrium) and the block can be maintained with the HFAC waveform.

Vertigo Reversible ENCB can be applied to the neural structure of the inner ear to treat vertigo. For example, dizziness can be caused by Meniere's disease, which causes inner ear disorders (which can occur in one or two ears) where spontaneous dizziness develops. Traditionally, dizziness can be treated by making an incision in the vestibular nerve. Dissection of the vestibular nerve includes identifying and dissecting the vestibulocochlear nerve in the inner ear while avoiding the cochlear nerve that extends adjacent to the vestibulocochlear nerve. Advantageously, ENCB can be used to produce similar effects, but ENCB is completely reversible and deaf (which occurs during about 20% vestibular nerve resection). Eliminate any permanent side effects, including. ENCB is fully applied (eg, controlled as a closed loop by one or more sensors, or controlled as an open loop by a physician) and, as needed, continuously or intermittently (eg, controlled by a physician). It can be applied to one or both ears (controlled by the patient or physician as an open loop).

To avoid blocking the cochlear nerve, ENCB can be transmitted by electrode contacts located distally. Alternatively, the nerve cuff electrode can be placed directly around the vestibular nerve branch to allow the ENCB to be transmitted and block the entire vestibular nerve. Insulation around the nerve cuff electrodes can prevent current from being transmitted to the adjacent cochlear nerve and maintain hearing during the vestibular nerve block period. Alternatively, nerve cuff electrodes can be placed around the entire vestibular nerve, reducing dizziness by applying ENCB, but resulting in overt hearing loss. However, hearing loss is temporary because ENCB is reversible.

ENCB can be realized by a plurality of methods. In some cases, charge-balanced or unbalanced HFAC waveforms (voltage or current control) can be used to generate rapidly induced and rapidly reversible neural conduction blocks. A typical waveform frequency can be between 5 and 50 kHz. The waveform may be continuous or interrupted, and each pulse can have a variety of shapes, including squares, triangles, sinusoids, and the like.

In other cases, a charge-balanced DC waveform that decreases the current to the opposite polarity, including increasing to a plateau of one polarity that can last for a period of time (eg, 10 seconds), can be used for ENCB. The plateau of each phase may be the same, but usually the second phase is 10-30% of the width of the first phase. Total charge transmission is zero or substantially less than the charge in each phase (eg, less than 10% charge imbalance). The waveform produces depolarized or hyperpolarized nerve blocks during the first phase plateau and, in some cases, also during the second phase plateau. The current is often increased from zero to a slow plateau within seconds to eliminate the generation of action potentials in the nerve. Further, by cycling between different contacts using a plurality of electrode contacts, a DC waveform can be transmitted to a nerve to maintain a constant conduction block.

In other cases, DC and HFAC waveforms can be combined to generate nerve blocks with the desired characteristics of each type of ENCB. A charge-balanced DC can first be established and used to block an initial reaction from HFAC that normally lasts several seconds. When the initial reaction is complete, the charge equilibrium DC waveform can be terminated (usually after charge equilibrium) and the block can be maintained with the HFAC waveform.

Salivation Salivation or excessive salivation is one of the major problems in children with cerebral palsy and is associated with neurodegenerative diseases. Conventional medical management uses topical drugs, oral drugs and botulinum toxim, which is not preferable. This is because these treatments are ineffective or produce unwanted side effects, including lack of salivation when desired. Advantageously, ENCB can be used as an alternative to these traditional treatments, which can quickly and reversibly block the activation of salivary glands, so that saliva can be used when needed. Reduce production. Benefits of ENCB include the ability of the patient or nurse to turn off salivary gland activation as needed. It should be noted that ENCB provides partial or incomplete blocking and reduces, but not eliminates, salivation secretion, so that symptoms can be alleviated without unwanted side effects.

ENCBs for targeting one or more nerves and alleviating salivary secretion can be applied to nerve branches that provide autonomous activation of salivary glands. Alternatively, the linear electrode with one or more contacts can be placed adjacent to the target nerve to produce the desired block. Such a method can simplify the installation of surgery. ENCB can be applied directly to or near each salivary gland.

ENCB can be realized by a plurality of methods. In some cases, charge-balanced or unbalanced HFAC waveforms (voltage or current control) can be used to generate rapidly induced and rapidly reversible neural conduction blocks. A typical waveform frequency can be between 5 and 50 kHz. The waveform may be continuous or interrupted, and each pulse can have a variety of shapes, including squares, triangles, sinusoids, and the like.

In other cases, a charge-balanced DC waveform that decreases the current to the opposite polarity, including increasing to a plateau of one polarity that can last for a period of time (eg, 10 seconds), can be used for ENCB. The plateau of each phase may be the same, but usually the second phase is 10-30% of the width of the first phase. Total charge transmission is zero or substantially less than the charge in each phase (eg, less than 10% charge imbalance). The waveform produces depolarized or hyperpolarized nerve blocks during the first phase plateau and, in some cases, also during the second phase plateau. The current is often increased from zero to a slow plateau within seconds to eliminate the generation of action potentials in the nerve. Further, by cycling between different contacts using a plurality of electrode contacts, a DC waveform can be transmitted to a nerve to maintain a constant conduction block.

In other cases, DC and HFAC waveforms can be combined to generate nerve blocks with the desired characteristics of each type of ENCB. A charge-balanced DC can first be established and used to block an initial reaction from HFAC that normally lasts several seconds. When the initial reaction is complete, the charge equilibrium DC waveform can be terminated (usually after charge equilibrium) and the block can be maintained with the HFAC waveform.

Refractory hiccups By blocking the phrenic nerve conduction, ENCB can be used to relieve refractory hiccups. For example, the hiccups that are about to occur can be detected by neural signals recorded in the proximal phrenic nerve. Many activities that indicate hiccups that are about to occur can be used to induce ENCB more distally in the phrenic nerve. In some embodiments, the block is applied only for a very short period of time to prevent hiccups so as not to interfere with normal breathing. The ENCB can include, for example, a DC waveform (via electrode contacts of high-strength material), where the DC waveform is followed by the HFAC waveform.

The above description and examples are merely for explaining the present invention by way of examples, and do not limit the present invention. For example, ENCB can be used for the treatment of other disorders, such as asthma complications (open airways) or Parkinson's disease complications. Each of the embodiments and examples disclosed in the present disclosure may be considered individually or in combination with other embodiments, examples and variations of the present disclosure. It should be noted that some features of the embodiments of the present disclosure are shown only in specific figures, but these features can be incorporated into other drawings to show other embodiments and are still disclosed. Is included in the range of. Also, unless otherwise stated, the steps of the method of the invention are not limited to any particular order of execution. Changes to the disclosed embodiments incorporating the spirit and content of the present disclosure will be conceivable to those skilled in the art, and such changes are within the scope of the present disclosure. All references cited herein are incorporated by reference in their entirety.

Claims (8)

It ’s a system,
It has a controller, a waveform generator, and electrical contacts.
The controller is arranged to receive an input associated with a desired change in the electrical nerve conduction block (ENCB), the input indicating at least one parameter associated with the ENCB to be modified.
The waveform generator is connected to the controller to receive a signal based on the input and is arranged to generate a DC waveform using at least one parameter associated with the ENCB, the DC waveform causing pain. Arranged to block the transmission of nerve signals that cause
The electrical contacts are connected to the waveform generator and are arranged to transmit the DC waveform to the nerve to block the transmission of the nerve signal that causes pain.
The electrical contacts are arranged in contact with nerves, the electrical contacts include a high charge capacitance material, the high charge capacitance material is a damaging electrochemical reaction with charges transmitted by a DC waveform by the ENCB. A system that prevents product formation and the high charge capacitance material has a charge injection capacitance of ^{1-5 mC / cm 2} . The system according to claim 1, wherein the controller forms a part of an open loop control system. The system according to claim 2, wherein the controller is arranged to receive the input from the user in order to adjust the ENCB. The system according to claim 1, wherein the controller forms a part of a closed loop control system. The system of claim 4, wherein the controller is arranged to receive the input from a sensor that senses changes in physiological parameters in order to adjust the ENCB. The controller, as appropriate ENCB is generated, the timing parameter based on the input, strength parameters, any one of claims 1 to 5, characterized in that it is arranged to specify the waveform parameters The system described in. The ENCB according to any one of claims 1 to 6 , wherein the ENCB includes at least one of a single-phase direct current (DC) waveform, a charge-balanced direct current (CBDC) waveform, and a substantial CBDC waveform. System. Said waveform generator, so as to recover the normal signal transmission through the nerve and transmission ENCB stops, of claims 1 to 7, characterized in that it is arranged to produce a reversible ENCB The system according to any one item.

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