WO2019246318A1

WO2019246318A1 - Systems and methods for thermal blockade of nerves

Info

Publication number: WO2019246318A1
Application number: PCT/US2019/038065
Authority: WO
Inventors: Stephen POPIELARSKI; Changfeng Tai; Grant Chapman
Original assignee: Thermaquil, Inc.; University Of Pittsburgh - Of The Commonwealth System Of Higher Education
Priority date: 2018-06-19
Filing date: 2019-06-19
Publication date: 2019-12-26
Also published as: AU2019288384A1; EP3810003A1; CA3104484A1; CN112566572A; EP3810003A4; JP2021528151A

Abstract

The present disclosure generally pertains to systems and methods for reversible blockade of nerves using thermal energy including heating and cooling. Heating and/or cooling elements may be implantable with additional components of the system provided external to the body. The system may also be completely implantable or completely external to the body.

Description

SYSTEMS AND METHODS FOR THERMAL BLOCKADE OF NERVES

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Patent Application No. 62/686,712 entitled, “Devices, Uses and Methods for Reversible Nerve Block at Moderate Temperature,” and filed on June 19, 2018, and its contents are incorporated fully herein by reference.

[0002] The present application also incorporates by reference in its entirely published PCT application no. PCT/US2016/064364 entitled“Device and Method for Nerve Block by Local Cooling to Room Temperature,” filed on December 1 , 2016.

STATEMENT REGARDING FEDERALLY SPONSORED

RESEARCH OR DEVELOPMENT

[0003] This invention was made with Government support under DK068566, DK094905,

DK102427, and DK1 1 1382 awarded by the National Institutes of Health. The Government has certain rights in the invention.

FIELD OF THE INVENTION

[0004] The field of the invention is reversible nerve blockade by thermal energy in humans and animal subjects.

BRIEF DESCRIPTION OF THE DRAWINGS [0005] The disclosure can be better understood with reference to the following drawings. The elements of the drawings are not necessarily to scale relative to each other, emphasis instead being placed upon clearly illustrating the principles of the disclosure. Furthermore, like reference numerals designate corresponding parts throughout the several views.

[0006] FIGS. 1A-B are block diagrams illustrating exemplary embodiments of a thermal energy system for reversible blockade of nerve conduction.

[0007] FIG. 2 is a block diagram illustrating an additional exemplary embodiment of a thermal energy system for reversible blockade of nerve conduction.

[0008] FIGS. 3A-C illustrate an exemplary thermal energy system for reversible blockade of nerve conduction.

[0009] FIG. 4 is a block diagram illustrating another exemplary embodiment of a thermal energy system for reversible blockade of nerve conduction.

[0010] FIGS. 5A-B are images of another exemplary thermal energy system, such as is depicted by FIG. 4, for reversible blockade of nerve conduction.

[0011] FIGS. 6A-B depict exemplary effects of distance on heated or cooled nerve or tissue temperature, as may be provided by a thermal energy system.

[0012] FIG. 7 illustrates an exemplary insertion sheath, as can be used to aid the implantation of components of a thermal energy system, such as the embodiment depicted by FIG. 5A.

[0013] FIG. 8 is a rear perspective view of an exemplary fluidic neural interface without connection to fluid tubing.

[0014] FIG. 9 is a section view of an embodiment of an exemplary fluidic neural interface, such as depicted in FIG. 8, around a nerve surrounded by a conductive gel, as further surrounded by insulation.

[0015] FIGS. 10A-B are additional section views of an embodiment of an exemplary fluidic neural interface, such as depicted in FIG. 8. [0016] FIG. 1 1 is a front perspective view schematic of an exemplary fluidic neural interface, such as depicted in FIG. 8, around a nerve, with the fluid channels extending to the rear.

[0017] FIGS. 12A-B are perspective views of an exemplary fluidic neural interface, such as depicted in FIG. 8, with fluid tubing attached (12A) or not attached (12B)

[0018] FIG. 13A, 13B and 13C are three portions of a flow chart depicting exemplary methods for applying blockade aspects as described herein.

[0019] DETAILED DESCRIPTION

[0020] The present invention relates to a series of methods and devices for thermally modulating nerves in the body of a human or other mammal. The invention may be especially helpful for reversible blockade of chronic pain.

[0021 ] Embodiments of the present disclosure are illustrated by way of example in FIGS. 1 - 13. It should be noted that all terms as used herein are given their common meaning as known in the art and as further described and discussed hereafter. In this specification, and in the claims that follow, reference is made to a number of terms that shall be defined to have the following meanings:

[0022] As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly indicates otherwise.

[0023] As used herein, ranges can be expressed as from "about" one particular value, and/or to "about" another particular value. When such a range is expressed, an embodiment includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by the use of "about," it will be understood that the particular value forms another embodiment. It will be understood that the endpoints of each of the ranges are significant both in relation to the other endpoint and independently of the other endpoint. It will also be understood that there are a number of values disclosed herein, and that each value is also disclosed herein as "about" that particular value in addition to the value itself. For example, if the value "50" is disclosed, then "about 50" is also disclosed. [0024] As used herein,“moderate cooling” means cooling below body temperature to a level and for a duration in which any nerve damage that may occur is considered to be reversible. For example, moderate cooling includes cooling at a temperature ranging from about 15°C to about 30°C.

[0025] As used herein,“moderate heating” means heating above body temperature to a level and for a duration in which any nerve damage that may occur is considered to be reversible. For example, moderate heating may include heating at a temperature ranging from about 42°C to about 48°C for a duration not exceeding about 5-10 minutes.

[0026] As used herein, “reversible” means the ability for a nerve with a partial or complete blockade to regain the majority of useful nerve function within a period of about one month following the blockade-inducing treatment. By this definition of “reversible”, ablation is not considered to be reversible.

[0027] As used herein, the terms "treatment" or "treating" include any desirable effect on the symptoms or pathology of a disease or condition, and may include even minimal reductions in one or more measurable markers of the disease or condition being treated. "Treatment" does not necessarily indicate complete eradication or cure of the disease or condition, or associated symptoms thereof.

[0028] As used herein, the terms “patient” or “subject” includes any mammal, including humans.

[0029] As used herein, the terms“communicate”,“communication”, or“communicating” refer to the transfer, transmission, sending, and receipt of data, including signals, input, commands, and output. A device, component, or system may communicate with another or several other devices, components, or systems either directly through a physical connection or indirectly, such as through wireless transmission. Data that is communicated may be converted, translated, or otherwise processed between devices, components, or systems. The terms “communicate”, “communication”, or “communicating” may additionally refer to the transmission, transfer, circulation, or movement of fluid from one or several devices, components, or systems to another or several other devices, components, or systems. Any electronic or fluidic communication means known in the art are contemplated.

[0030] As used herein, the“blockade” of a nerve refers to situations where the neurons do not propagate action potentials or have reduced amplitudes of evoked action potentials. A blockade of a nerve may be partial, where a lower percentage of neurons propagate action potentials than do neurons which are not blocked or when amplitudes of evoked action potentials are reduced relative to amplitudes of action potentials evoked by neurons which are not blocked.

[0031] As used herein, the“internal” location of components, devices, or systems is relative to the human body. For instance, a device located internally may be located within the patient’s body or under the skin of a patient.

[0032] As used herein, the“external” location of components, devices, or systems is relative to the human body. For instance, a device located externally many be located outside the body of the patient or on the body of the patient, but not within the patient’s body or under the skin of a patient.

[0033] In aspects, provided herein are methods and devices for reversibly stimulating and/or blocking a nerve via thermal modulation. Blocking a nerve may be useful in the treatment of many conditions including without limitation blockade and/or stimulation of the occipital nerve to treat for occipital neuralgia, the saphenous nerve for severe chronic knee pain following total knee replacement surgery, intra-articular region(s) of the knee to reduce pain associated with osteoarthritis, dorsal root ganglion and other regions of the spinal cord for severe chronic pain, any region along an incision site to treat post-operative pain following a procedure or around a painful wound, or the median nerve, ilioinguinal nerve, tibial nerve, sciatic nerve, intercostal nerve, peroneal nerve, femoral nerve, axillary nerve, suprascapular nerve, sural nerve, ulnar nerve, radial nerve, lateral femoral cutaneous nerve, or any other nerve that is causing pain. Other exemplary uses for the present methods and devices include treating obesity in a patient by blocking an abdominal branch of the vagus nerve, treating heart failure in a patient by blocking a sympathetic nerve, and optionally one or more of the greater splanchnic nerve, lesser splanchnic nerve, or sympathetic trunks, treating urinary retention in a patient by blocking a pudendal nerve, treating muscle spasms in a patient by means of a nerve innervating the muscle, treating cardiovascular disease in a patient by the vagus nerve, and treating occipital neuralgia or migraines in a patient by means of an occipital nerve. The present methods and devices are contemplated for use in the monitoring, diagnosis, or treatment of any such conditions or diseases wherein a nerve block is suitable for the analysis, identification, or management of the condition or disease or its symptoms.

[0034] In one embodiment, thermal modulation is selected from a group consisting of heating only, cooling only, alternation of heating and cooling, or heating and cooling simultaneously of the nerve. Exemplary methods and devices of heating only, cooling only, and alternation of heating and cooling are described herein.

[0035] The reversible thermal blockade achieved by the present invention may in some embodiments be accomplished by moderately heating and then moderately cooling a defined section of a nerve. It is well known that extreme heating or cooling of a nerve over longer durations of time may lead to irreversible damage to that nerve. For instance, temperatures greater than or equal to about 50°C and less than or equal to about 5°C have been used in methods known in the art for single-temperature nerve blocks. However, applying these extreme temperatures to a nerve may cause permanent damage within minutes or hours.

[0036] The initial heating step may allow for higher cooling temperatures to be applied to generate a complete or partial nerve blockade than would otherwise be possible or acceptable without the initial heating step. The present invention may avoid the use of potentially permanent damage-inducing extreme temperatures by the combination of the initial moderate heating and subsequent moderate cooling steps. Blockade of the nerve includes situations where the neurons treated according to the present methods or with the present devices do not propagate action potentials or a lower percentage of neurons propagate action potentials than do neurons which are not blocked.

[0037] The present invention may affect nerves at safe temperatures where at least partially irreversible nerve damage is avoided. The present invention may avoid use of these extreme and potentially damaging temperatures by first heating a nerve at a moderate temperature for a duration of time at a temperature above body temperature but below a temperature in which irreversible damage may be done to the nerve over said duration. During moderate heating, nerve conduction may be partially or completely reduced and nerves may be observed to have a partially or completely reduced evoked action potential or signal. Following moderate heating of the nerve, moderate cooling may be administered for a duration of time at a temperature below body temperature but above a temperature in which irreversible damage may be done to the nerve over said duration. During moderate cooling, the temperature may be held at a cooling temperature or may be reduced in a series of steps of decreasing cooling temperatures. Said steps may be of equal or unequal duration and may be of equal or unequal magnitude of temperature. The transition between heating and cooling phases may occur in less than about one minute, between about one minute and about three minutes, or between about three minutes and about five minutes. In one embodiment, the transition in temperature between heating and cooling phases occurs between about five minutes and about 25 minutes. In one embodiment, the transition in temperature between heating and cooling phases occurs between about 25 minutes and about 60 minutes.

[0038] In one embodiment, the cooling phase is within a range of about -5°C to about 0°C. In one embodiment, the cooling phase is within a range of about 0°C to about 15°C. In one embodiment, the cooling phase is within a range of about 15°C to about 35°C. In one embodiment, the heating phase is within a range of about 40°C to about 51 °C. In one embodiment, the heating phase is within a range of about 43°C to about 48°C. [0039] In embodiments described in FIGS. 1A-B a thermal energy system (105, 305, 505) may be externally located relative to the patient, implanted into the patient, or have components located externally and internally at a location on or near a nerve for thermal modulation. As shown in FIG. 1A, a thermal energy system (105, 305, 505), may comprise a combination of internal and external components. In one embodiment, the combination of internal and external components may be utilized for heating, cooling, alternation of heating and cooling, or simultaneous heating and cooling of a nerve. In one embodiment, the thermal energy system (105, 305, 505) as in FIG. 1A may comprise a temperature controller (106, 306) comprising at least one heating element (108, 308, 515) and at least one cooling element (107, 307) implanted near a nerve, at least one feedback sensor (1 10, 310, 516), such as in one embodiment a temperature sensor capable of detecting temperature near at least one location, and an external system controller (109, 309, 510) connected to a power source. An internal temperature controller (106, 306) may comprise at least one heating element (108, 308, 515), at least one cooling element (107, 307), and at least one feedback sensor (1 10, 310, 516) such as in one embodiment a temperature sensor, as shown in FIG. 1A. In one embodiment, the system controller (109, 309, 510) may comprise a processor (1 1 1 , 311 , 522) and may communicate with the internal temperature controller (106, 306) capable of controlling the temperature of the at least one heating element (108, 308, 515) and the at least one cooling element (107, 307) and receiving information via signals from the at least one feedback sensor (1 10, 310, 516). The temperature may be adjusted by the system controller (109, 309, 510) based on the signals it receives from the at least one feedback sensor (1 10, 310, 516), including a temperature sensor.

[0040] In one embodiment, the at least one heating element (108, 308, 515) may be an electrical resistive heating element, an inductive heating element, a Peltier heater, microwave heating elements, radio frequency heating elements, and infrared emitters or any other suitable heating means capable of providing the heating temperatures and durations required in a moderate heating step in the thermal modulation of a nerve. In one embodiment, the at least one cooling element (107, 307) may be a coolant tube, a thermoelectric cooler, a refrigeration system, a Peltier cooler, ice, or any other suitable cooling means capable of providing the cooling temperatures and durations required in a moderate cooling step in the thermal modulation of a nerve. In one embodiment, feedback sensor (1 10, 310, 516) is a thermocouple, a thermistor or any other suitable device or material capable of monitoring the changes in temperature of a nerve before, during, and after thermal modulation to block or partially block the nerve. The feedback sensor (1 10, 310, 516), such as a temperature sensor, may be placed in or near the vicinity of the at least one heating element (108, 308, 515) or the at least one cooling element (107, 307), or at other locations in or on the body or elsewhere within the device.

[0041 ] In one embodiment, the at least one heating element (108, 308, 515) may comprise an electrical resistive heating element powered by inductive means. The electrical resistive heating element may comprise a flexible portion comprising at least one electrical resistive heating element powered by an inductive coil receiving radiated electromagnetic fields, said flexible portion connected to an internal control mechanism. The internal control mechanism may further comprise a temperature controller (106, 306) that may optionally communicate wirelessly with a system controller (109, 309, 510). The system controller (109, 309, 510) may be located internally or may be external in different embodiments.

[0042] In one embodiment, the at least one feedback sensor (1 10, 310, 516), such as in one embodiment a temperature sensor capable of detecting temperature, is located in at least one location selected from a group consisting of on or near the skin of a patient, on or near the at least one heating element (108, 308, 515), in or near one or more cooling fluid channels, or in or near a thermoelectric cooler. In one embodiment, a thermal energy system (105, 305, 505) may comprise one or more feedback sensors (1 10, 310, 516) for monitoring various biomarkers or biological signals for the purpose of modifying the thermal energy being directed to the nerve. The system controller (109, 309, 510) may receive and process biological signals of the subject from at least one feedback sensor (1 10, 310, 516). In one embodiment the feedback sensor (1 10, 310, 516) is a temperature sensor, but the feedback sensor (1 10, 310, 516) may also monitor the biological signals selected from a group consisting of temperature and chemical levels on or near a nerve. In one embodiment the feedback sensor (1 10, 310, 516) is a temperature sensor, but the feedback sensor (1 10, 310, 516) may also monitor the biological signals selected from a group consisting of body temperature, blood pressure, heart rate, time, perspiration, oxygen saturation, electrocardiogram signals, and/or any other such useful and suitable parameter of a patient’s health, symptoms, or comfort. In one embodiment there are a plurality of feedback sensors (1 10, 310, 516) whose output signals are received by the temperature controller (106, 306) and/or a processor (1 1 1 , 31 1 , 522) of the system controller (109, 309, 510) which are configured with software to control the cooling elements (107, 307) and the heating elements (108, 308, 515). The thermal energy system (105, 305, 505) is configured to communicate said parameters detected by said feedback sensor (1 10, 310, 516) with the system controller (109, 309, 510). The thermal energy system (105, 305, 505) in one embodiment is configurable by a clinician or the user after implantation or placement externally on a patient, by means of selecting one or more parameters in software or firmware on the system controller’s (109, 309, 510) processor (1 1 1 , 31 1 , 522) or on the temperature controller (106, 306). In another embodiment the parameters may be pre-set. In one embodiment, a user may control communication with the system controller (109, 309, 510) wherein a user may select input factors from a group consisting of pain level, extent of motor function, sensory sensitivity including pain touch, sharpness, temperature, and stress level. The user may also control the system by turning it“on” or“off or by varying the operation at any level. [0043] In one embodiment, the thermal energy system (105, 305, 505) may provide information to assist in the acceptable placement of the thermal energy system (105, 305, 505). In one embodiment, the thermal energy system (105, 305, 505) is configurable to assist in the acceptable placement of the thermal energy system (105, 305, 505) after partial or complete blockade of a nerve using a heating step followed by a cooling step. In this embodiment, the thermal energy system (105, 305, 505) may determine the acceptable placement of the thermal energy system (105, 305, 505) based on effects on a patient selected from a group comprising sensation, body temperature, blood pressure, heart rate, time, perspiration, oxygen saturation, electrocardiogram signals, temperature and chemical levels on or near a nerve, or any other such useful and suitable parameter of a patient’s health, symptoms, or comfort. In one embodiment, the placement of the thermal energy system (105, 305, 505) may be further guided by user input factors from a group consisting of pain level, extent of motor function, sensory sensitivity including pain touch, sharpness, temperature, and stress level. In one embodiment, a feedback loop may be utilized to control power delivered to the thermal energy system (105, 305, 505) based on temperatures detected by the feedback sensor (1 10, 310, 516) including without limitation a temperature sensor.

[0044] The temperature controller (106, 306) may be physically or wirelessly connected to a system controller (109, 309, 510) comprising a processor (1 1 1 , 31 1 , 522) for controlling the heating of the at least one heating element (108, 308, 515), the cooling of the at least one cooling element (107, 307), and monitoring temperature at the nerve. Means for wireless power transfer to the at least one heating element (108, 308, 515) may be inductive or microwave energy transfer.

[0045] In one embodiment, the thermal energy system (105, 305, 505) are powered by a power source, where the power source is selected from a group consisting of an internal primary battery, an internal (rechargeable) secondary battery, wireless power transfer including inductive power transfer, microwave wireless transfer, non-visible laser power transfer, alternating current, and kinetic energy harvesting systems.

[0046] In one embodiment, as shown in FIG. 2, a temperature controller (106, 306) of may be connected to the patient through open skin, such as through the use of a percutaneous wire and/or tube (312) or other such suitable connection means to control the internal components of the temperature controller (106, 306). In this embodiment of a thermal energy system (105, 305, 505), the percutaneous wire and/or tube (312) may be connected from an external system controller (109, 309, 510) comprising a processor (1 1 1 , 31 1 , 522) to at least one of the heating elements (108, 308, 515) or cooling elements (107, 307) and at least one feedback sensor (1 10, 310, 516) may communicate with the processor (1 1 1 , 31 1 , 522). In one embodiment, the at least one heating element (108, 308, 515) and/or at least one cooling element (107, 307) may be controlled by power received from the percutaneous wire (312) to a power source.

[0047] In various embodiments, such as those depicted in FIGS. 1A-B, fluid transport may be utilized to convey thermal energy of the thermal energy system (105, 305, 505) such that heating temperatures and cooling temperatures may be accurately reached as directed by the system controller (109, 309, 510). In one embodiment, a heat pipe is utilized to convey thermal energy of the thermal energy system (105, 305, 505) such that heating temperatures and cooling temperatures may be accurately reached as directed by the system controller (109, 309, 510). Said heat pipe may be flexible and may be constructed of a biocompatible material.

[0048] In one embodiment, as least one of the at least one heating element (108, 308, 515) or the at least one cooling element (107, 307) may comprise a channel (1 13) for circulating heated or cooled fluid. In one embodiment, a heated fluid reservoir (1 14) may be in communication with the channel (1 13) for circulating heated fluid. In one embodiment, cooled fluid reservoir (1 15) may be in communication with the channel (1 13) for circulating cooled fluid. Said heated fluid reservoir (1 14), said cooled fluid reservoir (1 15), or recycled fluid reservoir (512) may be capable of increasing or decreasing the temperature of the fluid within the reservoir rapidly, such that the fluid is capable of being circulated to provide heating and cooling of a nerve as directed by a system controller (109, 309, 510). While FIG. 1A shows a channel (1 13) for communicating cooled fluid to a cooled fluid reservoir (1 15) that connected to the at least on cooling element (107, 307), this is an exemplary embodiment and other channel configurations are possible, as described herein. For example, the channel (1 13) of FIG. 1A may be connected to the at least one heating element (108, 308, 515) for the communication of heated fluid with a heated fluid reservoir (1 14). In one embodiment, as described in FIG. 2, the at least one heating element (108, 308, 515) is heated by heated fluid and/or the at least one cooling element (107, 307) is cooled by cooled fluid received through a percutaneous tube (312) from at least one fluid reservoir communicating fluidly with at least one fluid pump controlled by the external system controller (109, 309, 510).

[0049] In one embodiment, the rapid increase or decrease in temperature of fluid within a heated fluid reservoir (1 14) and/or a cooled fluid reservoir (1 15) may be conducted using a thermal therapy device similar to that described in U.S. 9,283,109, which is hereby incorporated by reference in its entirety. Said device may further comprise a heat exchanger that heats and/or cools fluid and a pump for the movement of heated or cooled fluid. Other heat exchanging mechanisms capable of rapidly heating or cooling fluid in a heated fluid reservoir (1 14) and/or a cooled fluid reservoir (1 15) are contemplated in the present invention. Rapid increase or decrease may comprise a change of temperature of about 1 to about 10 degrees Celsius over a time of no greater than about 60 minutes, 25 minutes, five minutes, about three minutes, or preferably no greater than about one minute.

[0050] The thermal energy system (105, 305, 505) may be illustrated by FIGS. 3A-C, where

FIG. 3A depicts the relative scale of the implantable temperature controller (106, 306) of the one embodiment of thermal energy system (105, 305, 505) with a standard pencil tip as a reference. FIG. 3B depicts a view of the implantable components, which surround a target nerve. FIG. 3C shows details of the implantable components of the thermal energy system (105, 305, 505) located on or near a nerve. The at least one heating and/or cooling elements (108, 308, 515), (107, 307) provide thermal energy that is transferred along a conductive material (103) to heat or cool the nerve. In portions of the device not adjacent to the nerve, insulating material (104) surrounds the conductive material (103) to confine thermal energy transfer to the nerve and avoid transfer of thermal energy to non-target nerves. The entire device or a portion thereof may be coated with a biocompatible coating (102), such that the thermal energy system (105, 305, 505) may be implanted on or near a nerve for a duration of time necessary for treatment without triggering a significant immune response. In one embodiment, the at least one heating element (108, 308, 515) and the at least one cooling element (107, 307) are constructed in a shape, including the shape of a horseshoe, a C-shape, a bowl, and a semi-circle, as illustrated, by example, in FIGS. 3B-C. In one embodiment, the thermal energy system (105, 305, 505) is constructed of a biocompatible material or comprises a biocompatible coating on at least one segment of the device. Said biocompatible coating may be a gel, aerogel, hydrogel, microparticles, dermal or other filler, injectable slurry or other material of lower thermal conductivity than tissue or blood that does not produce a significant immune response. A biocompatible coating may be present on the thermal energy system (105, 305, 505) prior to implantation or may be coated on at least a portion of the thermal energy system (105, 305, 505) following implantation. Said biocompatible coating may be biodegradable and may degrade over a finite period of time. Said degradation may not occur in vivo or may only slowly degrade over an extended amount of time, such as a period of months or years, in vivo.

[0051] In one embodiment, the thermal energy system (105, 305, 505) is fully external and may further comprise a temperature controller (106, 306) comprising at least one heating element (108, 308, 515), at least one cooling element (107, 307), a system controller (109, 309, 510) comprising a processor (1 1 1 , 31 1 , 522), and at least one feedback sensor (110, 310, 516) such as in one embodiment a temperature sensor, as shown in FIG. 1 B. In one embodiment, the thermal energy system (105, 305, 505) is an external thermal energy system (105, 305, 505) for reversible blockade of a nerve in a subject. The external thermal energy system (105, 305, 505) may comprise a temperature controller (106, 306) comprising at least one heating element (108, 308, 515) and/or the at least one cooling element (107, 307) connected to a power source and to a temperature controller (106, 306), a system controller (109, 309, 510) and at least one feedback sensor (1 10, 310, 516), such as in one embodiment a temperature sensor capable of detecting temperature on or near at least one location. The external thermal energy system (105, 305, 505) may be configured to make a transition in temperature between a heating phase enabled by the at least one heating element (108, 308, 515) and a cooling phase enabled by the at least one cooling element (107, 307).

[0052] In one embodiment, the at least one heating element (108, 308, 515) may be an electrical resistive heating element, an inductive heating element, a Peltier heater, microwave heating elements, radio frequency heating elements, infrared emitters or any other suitable heating means capable of providing the heating temperatures and durations required in a moderate heating step in the thermal modulation of a nerve. In one embodiment, the at least one cooling element (107, 307) may be a coolant tube, a thermoelectric cooler, a refrigeration system, a Peltier cooler, ice, or any other suitable cooling means capable of providing the cooling temperatures and durations required in a moderate cooling step in the thermal modulation of a nerve. In one embodiment, feedback sensor (1 10, 310, 516) is a thermocouple, a thermistor or any other suitable device or material capable of monitoring the changes in temperature of a nerve before, during, and after thermal modulation to block or partially block the nerve. The feedback sensor (1 10, 310, 516), such as a temperature sensor, may be placed in or near the vicinity of the at least one heating element (108, 308, 515) or the at least one cooling element (107, 307) or at other locations in or on the body or elsewhere within the device.

[0053] In one embodiment, the at least one heating element (108, 308, 515) of thermal energy system (105, 305, 505) is an electrical resistive heating element comprising a flexible portion comprising at least one resistive heating element powered by an inductive coil receiving radiated electromagnetic fields, where the flexible portion is connected to an internal control mechanism. The internal control mechanism may comprise a temperature controller (106, 306) which may optionally communicate wirelessly with the system controller (109, 309, 510).

[0054] The temperature controller (106, 306) may be physically or optionally be wirelessly connected to a system controller (109, 309, 510) comprising a processor (1 11 , 31 1 , 522) for controlling the heating of the at least one heating element (108, 308, 515), the cooling of the at least one cooling element (107, 307), and monitoring temperature at the nerve. Said processor (1 1 1 , 31 1 , 522) may execute programming instructions that may be stored on the memory of the temperature controller (106, 306). The external thermal energy system (105, 305, 505) may include wireless power transfer to the at least one heating element (108, 308, 515), wherein the wireless power is inductive or microwave energy transfer.

[0055] The thermal energy system (105, 305, 505) and the system controller (109, 309, 510) are powered by a power source. The power source may be selected from a group consisting of internal primary battery, internal secondary (rechargeable) battery, wireless power transfer including inductive wireless power transfer, microwave wireless power transfer, non-visible laser power transfer, alternating current, and kinetic energy harvesting systems.

[0056] In one embodiment, the fully external thermal energy system (105, 305, 505) may be utilized to provide a method of reversible blockade of a nerve in a body of a subject by all external means utilizing all or a combination of the components of the external thermal energy system (105, 305, 505). In one embodiment, the thermal energy system (105, 305, 505) may reversibly block a nerve or nerves during a medical procedure for a duration of about a few minutes, for about a few hours or days, or for many years to treat chronic conditions or symptoms.

[0057] In one embodiment, the thermal energy system (105, 305, 505) is fully implantable and may further comprise a temperature controller (106, 306) comprising at least one heating element (108, 308, 515), at least one cooling element (107, 307), a system controller (109, 309, 510) comprising a processor (1 1 1 , 31 1 , 522), and at least one feedback sensor (110, 310, 516) such as in one embodiment a temperature sensor, as shown in FIG. 1 B. In one embodiment, the thermal energy system (105, 305, 505) is an implantable thermal energy system (105, 305, 505) for reversible blockade of a nerve in a subject. The fully implantable thermal energy system (105, 305, 505) may comprise a temperature controller (106, 306) comprising the at least one heating element (108, 308, 515) and/or the at least one cooling element (107, 307) implanted near or on the nerve and at least one feedback sensor (1 10, 310, 516) such as in one embodiment a temperature sensor capable of detecting temperature near at least one location, and a system controller (109, 309, 510) comprising a processor (1 1 1 , 31 1 , 522) connected to a power source.

[0058] In one embodiment, the at least one heating element (108, 308, 515) may be an electrical resistive heating element, an inductive heating element, a Peltier heater, microwave heating elements, radio frequency heating elements, infrared emitters or any other suitable heating means capable of providing the heating temperatures and durations required in a moderate heating step in the thermal modulation of a nerve. In one embodiment, the at least one cooling element (107, 307) may be a coolant tube, a thermoelectric cooler, a refrigeration system, a Peltier cooler, or any other suitable cooling means capable of providing the cooling temperatures and durations required in a moderate cooling step in the thermal modulation of a nerve. In one embodiment, feedback sensor (1 10, 310, 516) is a thermocouple, a thermistor or any other suitable device or material capable of monitoring the changes in temperature of a nerve before, during, and after thermal modulation to block or partially block the nerve. The feedback sensor (1 10, 310, 516), such as a temperature sensor, may be placed in or near the vicinity of the at least one heating element (108, 308, 515) or the at least one cooling element (107, 307) or at other locations in or on the body or elsewhere within the device.

In one embodiment, the at least one heating element (108, 308, 515) of thermal energy system (105, 305, 505) is an electrical resistive heating element comprising a flexible portion comprising at least one resistive heating element powered by an inductive coil receiving radiated electromagnetic fields, where the flexible portion is connected to an internal control mechanism. The internal control mechanism may comprise a temperature controller (106, 306) which may optionally communicate wirelessly with the system controller (109, 309, 510). The system controller (109, 309, 510) may be located internally or may be external in different embodiments.

[0059] The temperature controller (106, 306) may be physically or optionally be wirelessly connected to a system controller (109, 309, 510) comprising a processor (1 11 , 31 1 , 522) for controlling the heating of the at least one heating element (108, 308, 515), the cooling of the at least one cooling element (107, 307), and monitoring temperature at the nerve. Said processor (1 1 1 , 31 1 , 522) may execute programming instructions that may be stored on the memory of the temperature controller (106, 306). The thermal energy system (105, 305, 505) and the system controller (109, 309, 510) may be powered by a power supply. Wireless power transfer may occur between a power source and the at least one heating element (108, 308, 515), wherein the wireless power transfer includes inductive or microwave energy transfer.

[0060] In one embodiment, the fully implantable thermal energy system (105, 305, 505) may be utilized to provide a method of reversible blockade of a nerve in a body of a subject by all internal means utilizing all or a combination of the components of the internal thermal energy system (105, 305, 505). In one embodiment, the thermal energy system (105, 305, 505) may be reversibly block a nerve or nerves during a medical procedure for a time of about a few minutes, for about a few hours or days, or for many years to treat chronic conditions or symptoms.

[0061 ] In various fully implantable or fully external embodiments, the at least one feedback sensor (1 10, 310, 516), such as in one embodiment a temperature sensor capable of detecting temperature, is located in at least one location selected from a group consisting of on or near the skin of a patient, on or near the at least one heating element (108, 308, 515), in or near one or more cooling fluid channels, or in or near a thermoelectric cooler. In one embodiment, a thermal energy system (105, 305, 505) may comprise one or more feedback sensors (1 10, 310, 516) for monitoring various biomarkers or biological signals for the purpose of modifying the thermal energy being directed to the nerve. The system controller (109, 309, 510) may receive and process biological signals of the subject from at least one feedback sensor (1 10, 310, 516). In one embodiment the feedback sensor (1 10, 310, 516) is a temperature sensor, but the feedback sensor (1 10, 310, 516) may also monitor the biological signals selected from a group consisting of temperature and chemical levels on or near a nerve. In one embodiment the feedback sensor (1 10, 310, 516) is a temperature sensor, but the feedback sensor (1 10, 310, 516) may also monitor the biological signals selected from a group consisting of body temperature, blood pressure, heart rate, time, perspiration, oxygen saturation, electrocardiogram signals, and/or any other such useful and suitable parameter of a patient’s health, symptoms, or comfort. In one embodiment there are a plurality of feedback sensors (1 10, 310, 516) whose output signals are received by the temperature controller (106, 306) and/or a processor (1 1 1 , 31 1 , 522) of the system controller (109, 309, 510) which are configured with software to control the cooling elements (107, 307) and the heating elements (108, 308, 515). The thermal energy system (105, 305, 505) is configured to communicate said parameters detected by said feedback sensor (1 10, 310, 516) with the system controller (109, 309, 510). The thermal energy system (105, 305, 505) in one embodiment is configurable by a clinician or the user after implantation or placement externally on a patient, by means of selecting one or more parameters in software or firmware on the system controller’s (109, 309, 510) processor (1 1 1 , 31 1 , 522) or on the temperature controller (106, 306). In another embodiment the parameters may be pre-set. In one embodiment, the thermal energy system (105, 305, 505) may comprise a user controlling communication with the system controller (109, 309, 510) wherein the user may select input factors from a group consisting of pain level, extent of motor function, sensory sensitivity including pain touch, sharpness, temperature, and stress level. The user may also control the system by turning it“on” or“off or by varying the operation at any level.

[0062] In one embodiment, the thermal energy system (105, 305, 505) may provide information to assist in the acceptable placement of the thermal energy system (105, 305, 505). In one embodiment, the thermal energy system (105, 305, 505) is configurable to assist in the acceptable placement of the thermal energy system (105, 305, 505) after partial or complete blockade of a nerve using a heating step followed by a cooling step. In this embodiment, the thermal energy system (105, 305, 505) may determine the acceptable placement of the thermal energy system (105, 305, 505) based on effects on a patient selected from a group comprising body temperature, blood pressure, heart rate, time, perspiration, oxygen saturation, electrocardiogram signals, temperature and chemical levels on or near a nerve, and/or any other such useful and suitable parameter of a patient’s health, symptoms, or comfort. In one embodiment, the placement of the thermal energy system (105, 305, 505) may be further guided by user input factors from a group consisting of pain level, extent of motor function, sensory sensitivity including pain touch, sharpness, temperature, and stress level. In one embodiment, the feedback loop may be utilized to control power delivered to the thermal energy system (105, 305, 505) based on temperatures detected by the feedback sensor (1 10, 310, 516) including without limitation a temperature sensor. [0063] In various fully implantable or fully external embodiments, such as those described in FIG. 1 B, fluid transport may be utilized to convey thermal energy of the thermal energy system (105, 305, 505) such that heating temperatures and cooling temperatures may be accurately reached as directed by the system controller (109, 309, 510). In one embodiment, a heat pipe is utilized to convey thermal energy of the thermal energy system (105, 305, 505) such that heating temperatures and cooling temperatures may be accurately reached as directed by the system controller (109, 309, 510). Said heat pipe may be flexible and may be constructed of a biocompatible material.

[0064] In one fully implantable or fully external embodiment, as least one of the at least one heating element (108, 308, 515) or the at least one cooling element (107, 307) may comprise a channel (1 13) for circulating heated or cooled fluid. In one embodiment, a heated fluid reservoir (1 14) may be in communication with the channel (1 13) for circulating heated fluid. In one embodiment, cooled fluid reservoir (1 15) may be in communication with the channel (1 13) for circulating cooled fluid. Said heated fluid reservoir (1 14), said cooled fluid reservoir (1 15), or recycled fluid reservoir (512) may be capable of increasing or decreasing the temperature of the fluid within the reservoir rapidly, such that the fluid is capable of being circulated to provide heating and cooling of a nerve as directed by a system controller (109, 309, 510). While FIG. 1 B shows a channel (1 13) for communicating heated fluid to a heated fluid reservoir (1 14) that connected to the at least on heating element (108, 308, 515), this is an exemplary embodiment and other channel configurations are possible, as described herein. For example, the channel (1 13) of FIG. 1 B may be connected to the at least one cooling element (107, 307) for the communication of cooled fluid with a cooled fluid reservoir (1 15).

[0065] In several embodiments, a thermal energy system (105, 305, 505) is fully non- invasive and externally located or fully implantable. The at least one heating element (108, 308, 515) and at least one cooling element (107, 307) may each comprise a channel (1 13) in communication with a heated fluid reservoir (1 14) and a cooled fluid reservoir (1 15), respectively. The heated fluid reservoir (1 14) and a cooled fluid reservoir (1 15) may allow the rapid increase or decrease in fluid temperature, as directed by the system controller (109, 309, 510). Rapid increase or decrease may comprise a change of temperature of about 1 to about 10 degrees Celsius over a time of no greater than about five minutes, about three minutes, or preferably no greater than about one minute. In one embodiment, the rapid increase or decrease in temperature of fluid within a heated fluid reservoir (1 14) or a cooled fluid reservoir (1 15) may be conducted using a thermal therapy device similar to that described in U.S. 9,283,109, which is hereby incorporated by reference in its entirety. Said device may further comprise a heat exchanger that heats and/or cools fluid and a pump for the movement of heated or cooled fluid. Other heat exchanging mechanisms capable of rapidly heating or cooling fluid in the heated fluid reservoir (1 14) and a cooled fluid reservoir (1 15) are contemplated in the present invention.

[0066] In one embodiment, a hot temperature of fluid ranging from about 1 12°F to about

1 18°F is produced and transported from the heated fluid reservoir (1 15) to the at least one heating element (108, 308, 515), such that externally applied heated fluid may provide moderate heating to the nerve, as directed by the system controller (109, 309, 510). In one embodiment, a hot temperature of fluid ranging from about 1 12°F to about 1 14°F is produced and transported from the heated fluid reservoir (1 15) to the at least one heating element (108, 308, 515), such that externally applied heated fluid may provide initial moderate heating to the nerve, as directed by the system controller (109, 309, 510). A hot temperature of fluid ranging from about 1 15°F to about 1 17°F may then be produced and transported from the heated fluid reservoir (1 15) to the at least one heating element (108, 308, 515), such that externally applied heated fluid may provide increased moderate heating to the nerve, as directed by the system controller (109, 309, 510). The thermal energy system (105, 305, 505) may be placed directly against the skin of a patient or may include a layer of thermally-conducting gel to promote thermal energy transfer from the thermal energy system (105, 305, 505) to the patient.

[0067] A thermally conductive gel, self setting polymer, foam, plastic or other biocompatible polymer or composite material may be injected or inserted into the body such that the gel or material may increase the performance of the thermal energy system (105, 305, 505) by increasing thermal conductivity and the rate of thermal energy transfer in the area between a device and the target nerve. The thermally conductive gel or material may also spread thermal energy over a larger distance than it would otherwise be spread, which may allow many nerves to receive thermal energy. This spread of thermal energy may be useful in locations such as the intra-articular area of the knee or to thermally modulate nerves along a surgical site incision. Thermally conductive gels, foams, or other carrier materials are commonly made by combining a base polymer with a thermally conductive filler. Base polymers may include hydrogels and silicones, including gels that may be injected at room temperature and that set to their final shape in situ at body temperature. Fillers may include graphite, carbon fiber and ceramics, as are commonly used to create thermally conductive polymers with thermal conductivities in the range of 1 -40 W/mK, such as CoolPoly-D, CoolPoly Elastomers and CoolPoly-E materials commercially available by Celanese. Other thermally conductive gels or materials are contemplated for use with the present invention. The use of a thermally conductive gel or material can increase the performance of the thermal energy system (105, 305, 505) by increasing thermal conductivity and the rate of thermal energy transfer between a device and the target nerve. The thermally conductive gel or material can also spread thermal energy over a larger distance than it would otherwise be spread, which may allow many nerves to receive thermal energy. This spread of thermal energy may be useful in locations such as the intra-articular area of the knee. Other thermally conductive gels or materials are contemplated for use with the present invention. [0068] In one embodiment, a cold temperature of fluid ranging from about 6°C to about 10°C is produced and transported from the cooled fluid reservoir (1 15) to the at least one cooling element (107, 307), such that externally applied cooled fluid may provide moderate cooling to the nerve, as directed by the system controller (109, 309, 510). In one embodiment, the cold temperature of fluid may be about or greater than about 0°C and may increase in temperature to a range of about 6°C to about 10°C as desired for patient comfort.

[0069] In one embodiment, thermally conductive material may be perfused near the nerve prior to block or partially block a nerve using heating and cooling steps. In one embodiment, thermally insulating material may be perfused near the nerve prior to block or partially block axons of said nerve using heating and cooling steps.

[0070] In one embodiment of the invention, as shown by example in FIG. 4, a thermal energy system (105, 305, 505) comprises a temperature controller (106, 306) comprising at least one heating element (108, 308, 515) implanted near or on a nerve, a cooling element (107, 307) externally placed on the subject’s skin, at least one temperature sensor capable of detecting temperature near at least one location, and a system controller (109, 309, 510) connected to a power source or supply.

[0071 ] In one embodiment, the at least one heating element (108, 308, 515) may be an electrical resistive heating element, an inductive heating element, a Peltier heater, microwave heating elements, radio frequency heating elements, infrared emitters or any other suitable heating means capable of providing the heating temperatures and durations required in a moderate heating step in the thermal modulation of a nerve. In one embodiment, the at least one cooling element (107, 307) may be a coolant tube, a thermoelectric cooler, a refrigeration system, a Peltier cooler, ice, or any other suitable cooling means capable of providing the cooling temperatures and durations required in a moderate cooling step in the thermal modulation of a nerve. In one embodiment, the cooling element (107, 307) cools fluid conducted in one or more cooling fluid channels to an interface for the skin. In one embodiment, feedback sensor (1 10, 310, 516) is a thermocouple, a thermistor or any other suitable device or material capable of monitoring the changes in temperature of a nerve before, during, and after thermal modulation to block or partially block the nerve. The temperature sensor may be placed in or near the vicinity of the at least one heating element (108,

308, 515) or the at least one cooling element (107, 307) or at other locations in or on the body or elsewhere within the device.

[0072] In one embodiment, the at least one heating element (108, 308, 515) may comprise an electrical resistive heating element powered by inductive means. The at least one heating element (108, 308, 515) of the thermal energy system (105, 305, 505) may be an electrical resistive heating element comprising a flexible portion comprising at least one resistive heating element powered by an inductive coil receiving radiated electromagnetic fields. In one embodiment, the flexible portion of the thermal energy system (105, 305, 505) may be connected to an internal control mechanism comprising a temperature controller (106, 306), where said temperature controller (106, 306) may optionally communicate wirelessly with the system controller (109,

309, 510). The system controller (109, 309, 510) may be located internally or may be external in different embodiments.

[0073] In one embodiment, the at least one heating element (108, 308, 515) is heated by power received from a percutaneous wire to a power source. In one embodiment, the at least one heating element (108, 308, 515) is heated by heated fluid received through a percutaneous tube from a heated fluid reservoir communicating fluidly with a heated fluid pump controlled by the system controller (109, 309, 510).

[0074] In one embodiment, the at least one feedback sensor (1 10, 310, 516), such as in one embodiment a temperature sensor capable of detecting temperature, is located in at least one location selected from a group consisting of on or near the skin of a patient, on or near the at least one heating element (108, 308, 515), in or near one or more cooling fluid channels, or in or near a thermoelectric cooler. In one embodiment, a thermal energy system (105, 305, 505) may comprise one or more feedback sensors (1 10, 310, 516) for monitoring various biomarkers or biological signals for the purpose of modifying the thermal energy being directed to the nerve. The system controller (109, 309, 510) may receive and process the biological signals of the subject from the at least one feedback sensor (1 10, 310, 516). In one embodiment the feedback sensor (1 10, 310, 516) is a temperature sensor, but the feedback sensor (1 10, 310, 516) may also monitor the biological signals selected from a group consisting of temperature and chemical levels on or near a nerve. In one embodiment the feedback sensor (1 10, 310, 516) is a temperature sensor, but the feedback sensor (1 10, 310, 516) may also monitor the biological signals selected from a group consisting of body temperature, blood pressure, heart rate, time, perspiration, oxygen saturation, electrocardiogram signals, and/or any other such useful and suitable parameter of a patient’s health, symptoms, or comfort. In one embodiment there are a plurality of feedback sensors (1 10, 310, 516) whose output signals are received by the system controller (109, 309, 510) and/or a processor (1 1 1 , 31 1 , 522) of the system controller (109, 309, 510) which are configured with software to control the cooling elements (107, 307) and the heating elements (108, 308, 515). The thermal energy system (105, 305, 505) is configured to communicate said parameters detected by said feedback sensor (1 10, 310, 516) with the system controller (109, 309, 510). In one embodiment, the system controller (109, 309, 510) receives biological signals of the subject from at least one feedback sensor (1 10, 310, 516). The thermal energy system (105, 305, 505) in one embodiment is configurable by a clinician or the user after implantation or placement externally on a patient, by means of selecting one or more parameters in software or firmware on the system controller’s (109, 309, 510) processor (1 1 1 , 31 1 , 522). In another embodiment the parameters may be pre-set. In one embodiment, a user may control communications with the system controller (109, 309, 510) wherein the user may select input factors from a group consisting of pain level, extent of motor function, sensory sensitivity including pain touch, sharpness, temperature, and stress level. The user may also control the system by turning it“on” or“off” or by varying the operation at any level.

[0075] In one embodiment, the thermal energy system (105, 305, 505) may provide information to assist in the acceptable placement of the thermal energy system (105, 305, 505). In one embodiment, the thermal energy system (105, 305, 505) is configurable to assist in the acceptable placement of the thermal energy system (105, 305, 505) after partial or complete blockade of a nerve using a heating step followed by a cooling step. In this embodiment, the thermal energy system (105, 305, 505) may determine the acceptable placement of the thermal energy system (105, 305, 505) based on effects on a patient selected from a group comprising body temperature, blood pressure, heart rate, time, perspiration, oxygen saturation, electrocardiogram signals, temperature and chemical levels on or near a nerve, and/or any other such useful and suitable parameter of a patient’s health, symptoms, or comfort. In one embodiment, the feedback loop may be utilized to control power delivered to the thermal energy system (105, 305, 505) based on temperatures detected by the feedback sensor (1 10, 310, 516) including without limitation a temperature sensor.

[0076] The system controller (109, 309, 510) comprising a processor (1 1 1 , 31 1 , 522) may be physically or wirelessly connected to control electronics (513) for controlling the heating of the at least one heating element (108, 308, 515), the cooling of the at least one cooling element (107, 307), and monitoring temperature at the nerve. The system controller (109, 309, 510) may be implanted or external to the other components of the thermal energy system (105, 305, 505). Wireless power transfer may be used to provide power to the at least one heating element (108, 308, 515), wherein the wireless power transfer may include inductive or microwave energy transfer.

[0077] In one embodiment, the thermal energy system (105, 305, 505) are powered by a power source, where the power source is selected from a group consisting of an internal primary battery, an internal (rechargeable) secondary battery, wireless power transfer including inductive power transfer, microwave wireless transfer, non-visible laser power transfer, alternating current, and kinetic energy harvesting systems.

[0078] In one embodiment, a resistively heated implant (506) of a thermal energy system

(105, 305, 505) may be implanted on or near a nerve for the reversible blockade the nerve. In a preferred embodiment, as shown by way of example in FIG. 4, a resistively heated implant (506) of a thermal energy system (105, 305, 505) may be implanted on or near a nerve for the reversible blockade the nerve for heating. Said thermal energy system (105, 305, 505) may further comprise an external chiller pump (507) and a wearable device (508), including a system controller (109, 309, 510), an external cooling delivery device (509), and an inductive power supply (51 1). The inductively heated implant (506) may optionally comprise an echogenic guide (514), control electronics (513), at least one heating element (108, 308, 515) and at least one feedback sensor (1 10, 310, 516). The components of the thermal energy system (105, 305, 505) are described in detail below.

[0079] The resistively heated implant (506) may be implanted for a time of about a few minutes in order to block a nerve or nerves during a medical procedure, for about a few hours or days, or for many years to treat chronic conditions or symptoms. In one embodiment, the resistively heated implant (506) may be a thin, linear, and generally flexible implant, as shown by means of example in FIG. 5A. The resistively heated implant (506) may comprise a rigid portion (525) and a flexible portion (526). Said rigid portion (525) may house control electronics (513), including at least one positive thermal coefficient resistor element (519), a main inductive element (520), at least one power control MOSFET (518), a microcontroller (517) and supporting passive electronics (521), as required for operation. Said flexible portion (526) may house the at least one heating element (108, 308, 515) and the at least one feedback sensor (1 10, 310, 516) such as for sensing temperature. Said at least one heating element (108, 308, 515) and said at least one feedback sensor (1 10, 310, 516) may be components of at least one printed circuit board (PCB) (524). In one embodiment, the flexible portion (526) may include a flexible circuit comprising at least one PCB (524).

[0080] In one embodiment, the thermal energy system (105, 305, 505) or at least a section of at least a component of the thermal energy system (105, 305, 505) is constructed of a biocompatible material or comprises a biocompatible coating on at least one segment of the device. Said biocompatible coating may be a gel, aerogel, hydrogel, microparticles, dermal or other filler, injectable slurry or other material of lower thermal conductivity than tissue or blood that does not produce a significant immune response. A biocompatible coating may be present on the inductively heated implant (506) prior to implantation or may be coated on at least a portion of the inductively heated implant (506) following implantation. Said biocompatible coating may be biodegradable and may degrade over a finite period of time. Said degradation may not occur in vivo or may only slowly degrade over an extended amount of time, such as a period of months or years, in vivo.

[0081] In one embodiment, a thermal energy system (105, 305, 505) may comprise a feedback sensor (1 10, 310, 516) for monitoring the biological signals selected from a group consisting of temperature and chemical levels on or near a nerve. In one embodiment, a thermal energy system (105, 305, 505) may comprise a feedback sensor (1 10, 310, 516) for monitoring the biological signals selected from a group consisting of body temperature, blood pressure, heart rate, time, perspiration, oxygen saturation, electrocardiogram signal or any other such useful and suitable parameter of a patient’s health, symptoms, or comfort. The thermal energy system (105, 305, 505) may be capable of communicating said parameters detected by said feedback sensor (1 10, 310, 516) with the system controller (109, 309, 510). In one embodiment, a user may control communication with the system controller (109, 309, 510) wherein a user may select input factors from a group consisting of pain level, extent of motor function, sensory sensitivity including pain touch, sharpness, temperature, and stress level. The user may also control the system by turning it“on” or“off or by varying the operation at any level.

[0082] In one embodiment, the thermal energy system (105, 305, 505) may provide information to assist in the acceptable placement of the thermal energy system (105, 305, 505). In a preferred embodiment, the thermal energy system (105, 305, 505) may provide information to assist in the acceptable placement of the thermal energy system (105, 305, 505) after partially or completely blocking a nerve using a heating step followed by a cooling step. In this embodiment, the thermal energy system (105, 305, 505) may determine the acceptable placement of the thermal energy system (105, 305, 505) based on effects on a patient selected from a group comprising sensation, organ function, pain level, extent of motor function, temperature, sharpness, blood pressure, time, flow rate, heart rate, perspiration, stress level, or any other such useful and suitable parameter of a patient’s health, symptoms, or comfort. In one embodiment, the placement of the thermal energy system (105, 305, 505) may be further guided by user input factors from a group consisting of pain level, extent of motor function, sensory sensitivity including pain touch, sharpness, temperature, and stress level. In one embodiment, the feedback loop may be utilized to control power delivered to the thermal energy system (105, 305, 505) based on temperatures detected by the feedback sensor (1 10, 310, 516).

[0083] In one embodiment, the thermal energy system (105, 305, 505) includes a system controller (109, 309, 510), comprising a processor (1 1 1 , 31 1 , 522) in communication with the resistively heated implant (506), the external cooling delivery device (509), the inductive power source (51 1), and the external chiller pump (507). Description of the communications of the system controller (109, 309, 510) are detailed below.

[0084] In one embodiment, resistively heated implant (506) of the thermal energy system

(105, 305, 505) provides heat to a nerve as directed by a system controller (109, 309, 510) and is powered by radiated electromagnetic fields from the inductive power supply (51 1). In a preferred embodiment, a microcontroller (517) within the resistively heated implant (506) communicates with the system controller (109, 309, 510) and, after receiving a secure enable signal from the system controller (109, 309, 510), determines temperature set points, duration of heating, controls power flow to the at least one heating element (108, 308, 515), and directs other functions of the resistively heated implant (506), as required to reversibly block nerve. Said microcontroller (517) may be capable of wireless communication with said system controller (109, 309, 510) or may be physically connected to said system controller (109, 309, 510). Wireless communication may occur via Bluetooth connection or any other suitable wireless communication means. Extraneous wireless signals may not be recognized by the microcontroller (517), such that unintended heating events of the resistively heated implant (506) may be avoided.

[0085] In one embodiment, the inductive power supply (51 1) powers the resistively heated implant (506) as directed by the system controller (109, 309, 510). The inductive power supply (51 1) may be located relative to the resistively heated implant (506) such that it is capably of inductively powering said inductively heated implant (506). The microcontroller (517) of the inductively heated implant (506) may utilize the at least one power control MOSFET (518) or other solid state switch to limit the power transferred from the inductive power supply (51 1) to the at least one heating element (108, 308, 515). Said at least one power control MOSFET (518) may be pulse width modified. Said at least one power control MOSFET (518) may be utilized to gradually ramp power such that said at least one heating element (108, 308, 515) reaches its temperature set point. In a preferred embodiment, the temperature set point of the at least one heating element (108, 308, 515) is about 45°C. The microcontroller (517) is may be utilized to maintain a low power level and to direct the continued monitoring of the temperature during a cooling of a nerve. The microcontroller (517) may be in continuous communication with the system controller (109, 309, 510) to create a continuous feedback loop. Positive thermal coefficient resistor elements (519) may be utilized as a fail-safe system to limit the power to the inductively heated implant (506) in an analog fashion in the event of a malfunction. Built-in fuses within the at least one heating element (108, 308, 515) may protect said at least one heating element (108, 308, 515) against an overcurrent event and shut the at least one heating element (108, 308, 515) down in such an overcurrent event.

[0086] In one embodiment, the at least one heating element (108, 308, 515) may be an electrical resistive heating element, an inductive heating element, a Peltier heater, microwave heating elements, radio frequency heating elements, infrared emitters or any other suitable heating means capable of providing the heating temperatures and durations required in a moderate heating step in the thermal modulation of a nerve. In one embodiment, feedback sensor (1 10, 310, 516) is a temperature sensor, such as a thermocouple, a thermistor or any other suitable device or material capable of monitoring the changes in temperature of a nerve before, during, and after thermal modulation to block or partially block the nerve. The feedback sensor (1 10, 310, 516) may be placed in or near the vicinity of the at least one heating element (108, 308, 515) or at other locations in or on the body or elsewhere within the device. In one embodiment, an optional at least one echogenic guide (514) or other such suitable guiding material or device is located within the resistively heated implant (506) to aid in placement of said resistively heated implant (506).

[0087] In one embodiment, the cooling of the nerve by the thermal energy system (105, 305,

505) may be externally applied. In one embodiment, the cooling of the nerve is delivered by an external cooling delivery device (509) connected to an external chiller pump (507). The external cooling delivery device (509), inductive power supply (51 1), and the system controller (109, 309, 510) may be positioned at a target location, wherein said target location is against the skin that covers an implanted resistively heated implant (506) and its target nerve, as described in FIG 4 and shown by example in FIG. 5B. In a preferred embodiment, the external cooling delivery device (509), inductive power supply (51 1), and the system controller (109, 309, 510) are contained within a wearable device (508), such that the wearable device (508) may be positioned at a target location, wherein said target location is against the skin that covers an implanted resistively heated implant (506) and its target nerve. The wearable device (508) may be a patch, headband, strap, band, or any such means of containing said external cooling delivery device (509), inductive power supply (51 1), and the system controller (109, 309, 510) at said target location and providing thermal contact between the skin and said wearable device (508). In one embodiment, the wearable device (508) may be constructed from a soft conforming elastic material (for example, Shore Scale 25A) with straps or other such suitable means to conform to a target location of a patient. In one embodiment, a thin conforming thermally conductive elastomer, such as COOLPOLY® Thermally Conductive Plastic (Celanese, Ltd.) may coat a side of the wearable device (508) that contacts the skin of the patient such that the wearable device (508) may make thermal contact. In one embodiment, a thermally conductive gel may be used to improve the thermal contact with the wearable device (508). In a preferred embodiment, the wearable device (508) may be a headband positioned to treat conditions involving pain associated with the occipital nerve.

[0088] The external cooling delivery device (509) of the thermal energy system (105, 305,

505) may administer the cooling of a nerve using chilling fluid provided by an external chiller pump (507). In one embodiment, the external cooling delivery device (509) and the external chiller pump (507) are contained within the wearable device (508). In a preferred embodiment, the external cooling delivery device (509) is contained within the wearable device (508) and connected to a separately located external chiller pump (507). The external cooling delivery device (509) and the external chiller pump (507) may be connected by a cooling fluid path, which may be insulated, such that chilling fluid may be directed from the external chiller pump (507) to the external cooling delivery device (509) at a target location and recycled fluid may be returned from the external cooling delivery device (509) to the external chiller pump (507) to be chilled. In one embodiment, the external chiller pump (507) may comprise a Peltier cooling system, such that recycled fluid may be chilled to become chilling fluid for reuse. The recycled fluid may be collected in a recycled fluid reservoir (512) of the external chiller pump (507), wherein the temperature of fluid within the recycled fluid reservoir (512) may increase or decrease rapidly, as directed by the system controller (109, 309, 510). In one embodiment, the system controller (109, 309, 510) may direct the external chiller pump (507) to control the chilling fluid temperature and flow rate within the cooling fluid path. The external chiller pump may comprise at least one feedback sensor (1 10, 310, 516) to monitor the temperature of chilling fluid, recycled fluid, and the temperature within the recycled fluid reservoir (512). Said at least one feedback sensor (1 10, 310, 516) may communicate with the system controller (109, 309, 510) to provide temperature measurements continuously or as directed by the system controller (109, 309, 510).

[0089] The recycled fluid and chilling fluid may be the same composition and located within the cooling fluid path of the thermal energy system (105, 305, 505). The only significant difference between the recycled fluid and the chilling fluid may be the temperature of each, and the recycled fluid and chilling fluid may be converted between each other by means of altering their temperatures. The composition of both the recycled fluid and the chilling fluid may be saline or any other suitable fluid such that the fluid may be chilled to a temperature required to cool a nerve without said fluid becoming frozen. In a preferred embodiment, the chilling fluid may be chilled to a temperature at or slightly below about 0°C, such that a nerve may be cooled to a temperature as directed by the system controller (109, 309, 510).

[0090] FIGS. 6A-B demonstrates the effects of distance on heating and cooling of a tissue.

In FIG. 6A, a cooling step requiring a nerve to be cooled to about 15°C is demonstrated using a simulation. In the simulation, it was determined that chilling fluid may provide a temperature of 0°C to the skin of a patient at a target location for about 10 minutes to effect a 15°C temperature for a nerve within 8 mm of the surface of the skin, while chilling fluid may provide a temperature of 0°C to the skin of a patient at a target location for about 20 to about 30 minutes to effect a 15°C temperature for a nerve within 20 mm of the surface of the skin. Beyond a depth of 20 mm from the surface of the skin, it may be impractical to externally cool a nerve as the required temperature of the chilling fluid may be uncomfortable or intolerable for a patient and may require extraneous energy to produce. It was determined that, once a 15°C nerve cooled temperature is achieved, it may be possible to maintain the 15°C cooled temperature at the nerve with a chilling fluid at the skin surface of a patient with a temperature ranging from about 8°C to about 10°C. In FIG. 6B, an implanted resistively heated implant (506) is heated to 45°C at a depth of 20 mm within tissue, and the temperature of said tissue is monitored at varying distanced from the resistively heated implant (506). Heat from the resistively heated implant (506) remains about equal to the target temperature of 45°C, whereas the temperature of the tissue decreases several degrees with distance.

[0091] Insertion of a resistively heated implant (506) may be performed by any suitable insertion or surgical means known in the art. In one embodiment, insertion of an resistively heated implant (506) may be performed using an insertion device (535), as illustrated in FIG. 7. Said insertion device (535) may comprise an insertion sheath (538), a sheath control arm (537) and a plunger (536) and may be constructed of any material capable of being sterilized for insertion into a patient. The insertion sheath (538) may surround or otherwise encompass or incorporate the resistively heated implant (506) and guide said resistively heated implant (506) into a target location for insertion. The sheath control arm (537) may be pulled by a clinician, while said clinician holds the plunger (536), such that the insertion sheath (538) may be retracted, the resistively heated implant (506) may be exposed, and the insertion device (535) may be removed from the target site. The implanted resistively heated implant (506) may remain in its inserted target location.

[0092] In one embodiment, the thermal energy system (105, 305, 505) includes a thermal energy probe (405). The thermal energy probe (405) may be constructed in a shape including the shape of a horseshoe, a C-shape, a U-shape, a bowl, and a semi-circle, as illustrated by example in FIG. 8. The thermal energy probe (405) may be implanted at or near a nerve to provide heating and/or cooling, such that the nerve may experience reversible blockade. In one embodiment, the thermal energy probe (405) is U-shaped and extends around the nerve. The material of the thermal energy probe (405) may be constructed of any material which is thermally conductive and biocompatible when implanted at or near a nerve. In one embodiment, the thermal energy probe (405) is constructed of silver. The thermal energy probe (405) may be produced by 3D printing, injection molding, commercial casting processes, or any other suitable production technique.

[0093] The thermal energy probe (405) may be sized such that it scales with the diameter of the nerve, such that the thermal energy probe (405) may extend around the nerve or extend a particular distance along the nerve, as desired for reversible blockade of the nerve. In one embodiment, a U-shaped thermal energy probe (405) surrounds a nerve on three out of four sides from a planar on-axis view, as shown in FIG. 9, such that an even temperature distribution may be maintained throughout at lease a section of the nerve. The cross sectional parameters of a thermal energy probe (405) may thus be determined by the diameter of the nerve it may target for reversible blockade. The thermal energy probe (405) may be of millimeter-scale dimensions including, for instance, 4 mm by 3 mm by 5 mm thermal energy probe (405) for a 2 mm diameter and 2 mm axial section of a nerve.

[0094] In one embodiment, the size of the thermal energy probe (405) may be calculated from the dimensions of a target nerve according to Equations (1)-(4) with reference to the dimensions in FIGS. 10A-B:

X1 = D + 1.5 mm (1)

X2 = X1 + 2 mm (2)

Y = D + 2 mm (3)

Z = Zn + 1.5 mm (4) [0095] In Equation (1), X1 is a dimension of a U-shaped thermal energy probe (405) as shown in FIG. 10A. The diameter of a nerve is D. In Equation (2), X1 is a dimension of a U- shaped thermal energy probe (405) as shown in FIG. 10A. In Equation (3), Y is a dimension of a U-shaped thermal energy probe (405) as shown in FIG. 10A. In Equation (4), Z is a dimension of a U-shaped thermal energy probe (405) as shown in FIG. 10B. The axial length of a target nerve is Zn.

[0096] In one embodiment, the thermal energy probe may further comprise at least one fluid channel (406), such that heated fluid or cooled fluid may enter the thermal energy probe (405) and transfer thermal energy to the thermal energy probe (405) for heating or cooling the nerve. The at least one fluid channel (406) may have a diameter of about 0.3 mm or any diameter suitable for a snug fit of tubing (407). The at least one fluid channel (406) may be about 1.5 mm in length, or any other suitable length such that tubing (407) may be securely held in place and such that thermal energy probe (405) size is minimized for implantation. The at least one fluid channel (406) may provide an inlet and an outlet for the heated fluid or cooled fluid and may be located on the back of the thermal energy probe (405), or in any suitable location as to provide the heated fluid or cooled fluid to the thermal energy probe (405). The heated fluid or cooled fluid may be water, saline, or any other suitable fluid such that the fluid may be heated or chilled to a temperature required to heat or cool a nerve without said fluid vaporizing or becoming frozen. The cooled or heated fluid may exit the thermal energy probe (405) through at least one fluid channel (406) which may serve as an outlet. In one embodiment, the cooled or heated fluid may be carried through the at least one fluid channel (406) using tubing (407), wherein the tubing (407) is flexible, insulated, and conforms to the dimensions of the at least one fluid channel (406) for a snug fit.

[0097] In one embodiment, the thermal energy probe (405) further comprises a coating of conductive gel (408) on a surface that is nearest the nerve as shown in FIGS 9-11. The conductive gel (408) may be used to cushion the nerve within the thermal energy probe (405) and may promote thermal energy transfer from the thermal energy probe (405) to the nerve. The conductive gel (408) may further act to maintain a low level of temperature variance throughout the at least one section of a nerve. Higher thermally conductivities of the conductive gel (408) may result in more efficient thermal energy transfer from the thermal energy probe (405). The conductive gel (408) may be biocompatible for implantation at or near a nerve. Other thermally conductive gels or materials are contemplated for use with the present invention.

[0098] In one embodiment, the thermal energy probe (405) may comprise an insulation backing (409) on at least one surface of the thermal energy probe (405) that does not interface with a nerve. The insulation backing (409) may comprise a solid material that conforms to the features of the thermal energy probe (405) and is insulating with a low thermal conductivity. In one embodiment, the insulation backing (409) is made of polyurethane and the thermal conductivity of the insulation backing (409) is about 0.027 W/mK. The insulation backing (409) may be placed on a back surface of the thermal energy probe (405) and may conform to features, such as the at least one fluid channel (406). The insulation backing (409) may prevent the loss of thermal energy from the thermal energy probe (405). The thermal energy probe (405) with insulation backing (409) is shown in FIG. 1 1.

[0099] In one embodiment, the thermal energy probe (405) is implanted at or near a nerve for reversible blockade. The placement of the thermal energy probe (405) may be guided by ultrasound and inserted through an incision using an applicator or other such suitable device for placing the thermal energy probe (405). The thermal energy probe (405) may be positioned such that the nerve is cushioned by the conductive gel (408) coating a surface of the thermal energy probe (405). In the instance where a U-shaped thermal energy probe (405) is used, the conductive gel (408) may be coated on the inside of the U feature. In one embodiment, insulating material (410) may be injected or placed around the thermal energy probe (405) during insertion. The insulating material (410) may confine thermal energy transfer to a desired location and may aid in holding the thermal energy probe (405) in its location at or near the nerve. The insulating material (410) may be injected in a roughly spherical shape around the nerve and thermal energy probe (405) and may involve one or more injections to apply it to the desired location. In one embodiment, the insulating material (410) may be injected in a sphere with a 10 mm diameter. The insulating material (410) may be insulating and biocompatible and may be a liquid, gel, or foam. In a preferred embodiment, the insulating material (410) is a polyurethane foam with a thermal conductivity of about 0.027 W/mK. A low thermal conductivity of an insulating material (410) is desired. The insulating material (410) should have a viscosity that is low enough to allow for injection to the site but high enough to prevent it from leaving the target area after installation for some amount of time. An ideal insulating material (410) may be a self-setting material that is injected as a liquid and then undergoes a chemical reaction to solidify and set up to maintain its shape and location, such as CryoLife’s BioFoam Surgical Matrix.

[00100] A thermally insulating gel, self setting polymer, foam, plastic or other biocompatible polymer or composite material may be injected or inserted into the body such that the gel or material may direct or contain the heating and/or cooling of the thermal energy system (105, 305, 505) by decreasing thermal conductivity and the rate of thermal energy transfer in the area outside of the desired area of affect around a device and the target nerve. The thermally insulating gel or material may also prevent the spread of thermal energy over an area than it would otherwise be spread, which may allow more targeted use of thermal modulation or use of thermal modulation near and area where it is undesirable to thermally modulate. This containment of thermal energy may be useful in locations such as specifically targeting nerves in a joint that are causing discomfort without affecting nerves that control motion or sensation that are not causing pain. Thermally insulating gels, foams, or other carrier materials are commonly made by combining a base polymer with a thermally insulating filler. Base polymers may include hydrogels and silicones, including gels that may be injected at room temperature and that set to their final shape in situ at body temperature. Fillers may include polyurethane foams, polystyrene, glass fibers, and aerogels, as are commonly used to create thermally insulating polymers with thermal conductivities in the range of .1-.01 W/mK, such as polystyrene, Cabotcorp aero gel, and General Plastics corp polyurethane foam. Other thermally insulating gels or materials are contemplated for use with the present invention.

[00101] The thermal energy probe (405) may include locating hooks that may deploy after insertion, such that the thermal energy probe (405) is locked into the desired location at or near a nerve.

[00102] In one embodiment, the thermal energy probe (405) may be connected to components for controlling fluid flow and temperature. The components may be implanted or may be external to the patient. The components may include a pump, heat exchanger, thermal electric cooler, system controller (109, 309, 510), power source, and tubing (407). The pump may be used to transport heating or cooling fluid through the tubing (407) into the thermal energy probe (405), as shown in FIGS. 12A-B, and as directed by the system controller (109, 309, 510). The power source may be a battery or any other source of power suitable to power the components of the thermal energy system (105, 305, 505).

[00103] In one embodiment, the heat exchanger and thermal electric cooler are used to heat and cool fluid, respectively. In one embodiment, the heating fluid is about 42 C to about 54 C. In one embodiment, the cooling fluid is about 2 C to about 15 C. In a preferred embodiment, cooling fluid is about 15 C and heating fluid is about 50 C with a ±2 C on the surrounding tissue during heating and cooling. The system controller (109, 309, 510) may direct the heat exchanger and/or thermal electric cooler such that said temperatures may be maintained at the nerve. Fluid may be recycled back to the heat exchanger and/or thermal electric cooler from the thermal energy probe (405) for heating or cooling. In one embodiment, the flow rate of the heating or cooling fluid may range from about 0.0004 L/min to about 0.0001 L/min, depending on the temperature of the heating or cooling fluid. A pump may provide pressures of about 5 mbar to about 400 mbar to achieve these flow rates, depending on tubing (407) diameter. [00104] The device or system used for thermal modulation for reversible blockade may be adjusted based on pain type and duration and the depth of the nerve from the skin, as displayed by example in FIGS. 13A-C. In one embodiment, pain associated with a nerve may be chronic or acute, wherein chronic pain may be long-lasting and may occur over a duration of days, weeks, months, or years and acute pain may be of recent and/or sudden onset and may occur over a short duration of hours, days, weeks, or months. In one embodiment, chronic pain may occur over a duration of at least about three months. In one embodiment, acute pain may occur over a duration equal to or less than about two weeks. Chronic pain may include periods of remission or relapse and may affect one or more areas of the body. Acute pain may be severe and may affect one or more areas of the body. The chronic or acute pain may be persistent or sporadic, wherein persistent pain may occur continuously with one or more levels of severity and sporadic pain may occur intermittently with one or more levels of severity with regular or irregular episodes of pain. The device determination in FIGS. 13A-C is exemplary and methods for device selection and use may differ from patient to patient. The depth ranges of target nerves considered for various embodiments of the invention may differ from patient to patient and are exemplary in FIGS. 13A-C.

[00105] The selection of an implantable or an externally mounted heating element and/or cooling element (108, 308, 515), (107, 307) is based at least partially on the depth of the nerve and on the individual’s own sensory perceptions and tolerances to temperature. Sufficient heating of the nerve to initiate and maintain nerve block, for example nerve temperatures that approach about 40-45°C, can be generated externally by a heating element (108, 308, 515) to most patients when the depth of the nerve beneath the skin is less than or about 4 to 8 millimeters, in which case the heating element (108, 308, 515) may be preferentially external in this range unless a patient has particular sensitivity to warm temperatures or otherwise prefers to implant the heating element (108, 308, 515). Blocking nerves that are deeper than about 4 to 8 millimeters below the skin surface will generally require that the heating element (108, 308, 515) should be implanted so that when implanted it is within about 1 to 8 millimeters of the nerve. Sufficient cooling of the nerve to initiate and maintain nerve block, for example nerve temperatures in the range of about 15-30°C, can be generated externally through the skin by a cooling element (107, 307) when the depth of the nerve is no more than about 20 to 25 millimeters, so the cooling element (107, 307) optionally may be implanted or external for a nerve depth in this range. When the nerve is deeper than about 20-25 millimeters, then the cooling element (107, 307) and the heating element (108, 308, 515) should generally be implanted for maximum efficacy so that the cooling element (107, 307) is within about 20-25 millimeters of the nerve, and the heating element (108, 308, 515) is within about 4 to 8 millimeters of the nerve. These ranges may be shortened by the insertion of a thermally conductive material such as a gel, elastomer or other mixture between the heating and/or cooling element (108, 308, 515), (107, 307) and the nerve.

[00106] In one embodiment, as described by example in FIG. 13A, the thermal modulation includes reversible blockade for treatment of chronic, persistent pain (205). In this case, the response of the target nerve may be first tested in a clinical setting to determine its response to thermal modulation. Thermal modulation of the nerve may be tested in a clinical setting to evaluate the effectiveness of reversible blockade. In the case where the thermal modulation is successful, a thermal modulation device or system may be utilized either externally or as an implantable device. In a preferred embodiment, the thermal modulation may be applied from a fully implantable thermal system (206). In the case where thermal modulation is unsuccessful, thermal modulation may not be appropriate for treatment and other options may be explored (207).

[00107] In one embodiment, as described by example in FIG. 13A, the thermal modulation includes reversible blockade for treatment of chronic, sporadic pain (208). In one embodiment, the nerve is located at a depth of over about 20 mm from the skin of a patient (209). In this case, the response of the target nerve may be first tested in a clinical setting to determine its response to thermal modulation. In the case where the thermal modulation is successful, a thermal modulation device or system may be utilized either externally or as an implantable device. In a preferred embodiment where the nerve is located at a depth in the range of over about 20 mm from the skin of a patient, the thermal modulation may be applied from a fully implantable thermal system (206). In the case where thermal modulation is unsuccessful, thermal may not be appropriate for treatment and other options may be explored (207). In one embodiment, the nerve is located at a depth in the range of about 6 mm to about 20 mm from the skin of a patient (210). In this case, the response of the target nerve may be first tested in a clinical setting to determine its response to thermal modulation. In the case where the thermal modulation is successful, a thermal modulation device or system may be utilized either externally or as an implantable device. In a preferred embodiment where the nerve is located at a depth in the range of about 6 mm to about 20 mm from the skin of a patient, the thermal modulation may be applied with transcutaneous cooling (220) and implantable inductive heating device (219). In the case where thermal modulation is unsuccessful or partially successful, thermal may not be appropriate for treatment and other options may be explored (207). In one embodiment, the nerve is located at a depth of less than about 6 mm from the skin of a patient (21 1). In this case, the response of the target nerve may be first tested in a clinical setting to determine its response to thermal modulation. In the case where the thermal modulation is successful, a thermal modulation device or system may be utilized either externally or as an implantable device. In a preferred embodiment when the nerve is located at a depth of less than about 6 mm from the skin of a patient, the thermal modulation may be applied with a transcutaneous heating and cooling device (212). In the case where thermal modulation is unsuccessful or partially successful, thermal modulation may not be appropriate for treatment and other options may be explored (207).

[00108] In one embodiment, as described by example in FIG. 13B, the thermal modulation includes reversible blockade for treatment of acute, persistent pain (213). In one embodiment, the nerve is located at a depth of over about 20 mm from the skin of a patient (209) or in the range of about 6 mm to about 20 mm from the skin of a patient (210). In this case, the response of the target nerve may be first tested in a clinical setting to determine its response to thermal modulation. In the case where the thermal modulation is successful, a thermal modulation device or system may be utilized either externally or as an implantable device. In a preferred embodiment when the nerve is located at a depth of over about 20 mm from the skin of a patient or in the range of about 6 mm to about 20 mm from the skin of a patient, the thermal modulation device may be a temporary thermal probe (215) such that a physician may evaluate the need for continued thermal modulation as needed. In the case that thermal modulation continues to be needed (216), the device may continue to be utilized. In the case that thermal modulation is no longer needed (217), the device may be removed (218). In the case where thermal modulation is unsuccessful, thermal modulation may not be appropriate for treatment and other options may be explored (207). In one embodiment, the nerve is located at a depth of less than about 6 mm from the skin of a patient (21 1). In this case, the response of the target nerve may be first tested in a clinical setting to determine its response to thermal modulation. In the case where the thermal modulation is successful, a thermal modulation device or system may be utilized either externally or as an implantable device. In a preferred embodiment where the nerve is located at a depth of less than about 6 mm from the skin of a patient, the thermal modulation may be applied with a transcutaneous heating and cooling device (212). In the case where thermal modulation is unsuccessful or partially successful, thermal modulation may not be appropriate for treatment and other options may be explored (207).

[00109] In one embodiment, as described by example in FIGS. 13B-C, the thermal modulation includes reversible blockade for treatment of acute, sporadic pain (214). In one embodiment, the nerve is located at a depth of over about 20 mm from the skin of a patient (209). In this case, the response of the target nerve may be first tested in a clinical setting to determine its response to thermal modulation. In the case where the thermal modulation is successful, a thermal modulation device or system may be utilized either externally or as an implantable device. In a preferred embodiment where the nerve is located at a depth of over about 20 mm from the skin of a patient, the thermal modulation device may be a temporary thermal probe (215) such that a physician may evaluate the need for continued thermal modulation as needed. In the case that thermal modulation continues to be needed (216), the device may continue to be utilized. In the case that thermal modulation is no longer needed (217), the device may be removed (218). In the case where thermal modulation is unsuccessful, thermal or electrical modulation may not be appropriate for treatment and other options may be explored (207). In one embodiment, the nerve is located at a depth in the range of about 6 mm to about 20 mm from the skin of a patient (210). In this case, the response of the target nerve may be first tested in a clinical setting to determine its response to thermal modulation. In one embodiment, thermal modulation is tested in a clinical setting and the reversible blockade is evaluated. In the case where the thermal modulation is successful, a thermal modulation device or system may be utilized either externally or as an implantable device. In a preferred embodiment where the nerve is located at a depth in the range of about 6 mm to about 20 mm from the skin of a patient, the thermal modulation may be applied with a transcutaneous cooling (220) and implantable inductive heating device (219). In the case where thermal modulation is unsuccessful or partially successful, thermal modulation may not be appropriate for treatment and other options may be explored (207). In one embodiment, the nerve is located at a depth of less than about 6 mm from the skin of a patient (21 1). In this case, the response of the target nerve may be first tested in a clinical setting to determine its response to thermal modulation. In one embodiment, thermal modulation is tested in a clinical setting and the selective blockade is evaluated. In the case where the thermal modulation is successful, a thermal modulation device or system may be utilized either externally or as an implantable device. In a preferred embodiment where the nerve is located at a depth of less than about 6 mm from the skin of a patient, the thermal modulation may be applied with a transcutaneous heating and cooling device (212). In the case where thermal modulation is unsuccessful or partially successful, thermal modulation may not be appropriate for treatment and other options may be explored (207).

[001 10] In the case of a decision to utilize a thermal modulation device, a patient or other user may be trained or instructed on the use of said device. Thermal modulation may be administered using a thermal block. A thermal block may include the use of devices of varying degrees of implantation from fully external transcutaneous systems to fully implantable systems. For instance, a thermal block may include use of a thermal energy probe, a transcutaneous cooling and inductive powered heating device, a transcutaneous heating and cooling device, or a fully implantable thermal system.

[001 1 1 ] Further disclosed is method of selecting an affected area for thermal energy transfer between a thermal energy device for reversible blockade of an area around nerve in a body comprising mounting a heating element and/or a cooling element on or in the body near the nerve, inserting into the body a conductive gel or elastomer around the heating element and/or cooling element and the area around to be affected that may be near a nerve.

[001 12] Further disclosed herein is a method of selecting an affected area for thermal energy transfer between a thermal energy device for reversible blockade of an area around a nerve in a body comprising mounting a heating element and/or a cooling element on or in the body near the nerve, inserting into the body an insulating gel or elastomer around a desired affected area surrounding a heating element and/or cooling element to concentrate a thermal block between the desired affected area (consisting of the heating element and/or cooling element and the nerve) and the other areas of the body that it is desired not to affect the temperature .

[001 13] Methods of use of, devices that use, and uses of sensor data such as temperature, pressure, time and/or flow rate, and possibly but not necessarily including human input via machine interface as input to a feedback loop or algorithm to provide algorithmic control that will control outputs of the system/device described herein including but not limited to the pump flow rate or the temperature to which the Peltier electrode or other temperature controlling device is heated or cooled to change temperature as directed by algorithm control. The invention also includes other sources of data from wearable devices such as heartrate, extent of sweating, cardiac function/performance, blood pressure, stress level or GPS as non-exhaustive examples. Other sensors may be added to the device or included in the system’s inputs for the purpose of optimally controlling nerve conduction. The invention also includes algorithmic control over other outputs not specifically listed here that affect the operation or performance of the device in any way.

Claims

Claims We claim:

1. A method for determining for a patient a configuration of a thermal energy device for reversible blockade of a nerve in the patient’s body, comprising

a. determining a depth of the nerve inside the patient’s body, and b. determining whether a heating element and/or a cooling element of the thermal energy device should be implanted in or externally mounted on the body, according to the following ranges of depth:

i. for the range of depth of zero to about 4 to 7 mm, each of the heating element and the cooling element optionally may be externally mounted or implanted,

ii. for the range of depth of about 4 to 7 millimeters to about 20 to 25 mm, the heating element shall be implanted and the cooling element optionally may be externally mounted or implanted, or

iii. for the range of depth of about 20 to 25 mm or greater, the heating element and the cooling element shall be implanted.

2. A method of reversibly blocking a pain signal from being transmitted by a nerve in a body for reversible blockade, the method comprising

a. mounting a heating element and/or a cooling element on or in the body near the nerve,

b. inserting into the body a conductive polymer between the heating element and/or cooling element and the nerve, and

c. activating the heating element and/or the cooling element.

3. A thermal energy system for reversible blockade of a nerve in the body of a subject, the thermal energy system comprising

at least one heating element configured to be implanted near the nerve, at least one cooling element configured to be externally placed on skin of the subject,

at least one feedback sensor configured to detect temperature on or near at least one location,

a temperature controller and

a system controller, said system controller and said temperature controller connected to a power source and communicating with the feedback sensor and configured to control the heating element and the cooling element.

4. The thermal energy system as in claim 3, wherein the system controller and the temperature controller are configured to control the heating element and the cooling element based on a detected temperature received from the at least one temperature sensor and/or based on user inputs.

5. The thermal energy system as in claim 3 wherein the cooling element cools fluid conducted in one or more cooling fluid channels through the cooling element to an interface for the skin.

6 The thermal energy system as in claim 3 wherein the heating element is selected from a group consisting of an electrical resistive heating element, an inductive heating element, a Peltier heater, microwave heating elements, radio frequency heating elements and infrared emitters.

7. The thermal energy system as in claim 6 wherein the heating element comprises a flexible portion comprising the electrical resistive heating element powered by an inductive coil receiving radiated electromagnetic fields, said flexible portion connected to an internal control mechanism comprising the temperature controller, said temperature controller optionally communicating wirelessly with the system controller.

8. The thermal energy system as in claim 3 wherein the heating element is heated by heated fluid received through a percutaneous tube from a heated fluid reservoir communicating fluidly with a heated fluid pump controlled by the system controller.

9 A fully external thermal energy system for reversible blockade of a nerve in a subject, said fully external thermal energy system comprising

at least one heating element configured to be externally placed on skin of the subject,

at least one cooling element configured to be externally placed on the skin of the subject,

at least one feedback sensor capable of detecting temperature on or near at least one location proximate the nerve or in the system, a temperature controller, and

a system controller connected to a power source to the at least one feedback sensor, and to the temperature controller, said system controller and said temperature controller being configured to control said heating element and said cooling element to make a transition in temperature between a heating phase enabled by the heating element and a cooling phase enabled by the cooling element.

10. The fully external thermal energy system as in claim 9 wherein the transition between said heating and cooling phases occurs in less than one minute.

11. The external thermal energy system as in claim 9 wherein the cooling phase is within a range of 0°C to 15°C.

12. The fully external thermal energy system as in claim 9 wherein the cooling phase is within a range of 15°C to 35°C.

13. The fully external thermal energy system as in claim 9 wherein the system is contained within a headband wherein the at least one heating element and the at least one cooling element are positioned on the subject’s head near an occipital nerve.

14. A method of reversible blockade of a nerve in a body of a subject by all external means by any one of the systems in claims 9-13. A thermal energy system for reversible blockade of a nerve in the body of a subject, said thermal energy system comprising

at least one heating element configured to be implanted near the nerve, at least one cooling element configured to be implanted near the nerve, at least one feedback sensor configured to sense a detected temperature near at least one location,

an external system controller,

a temperature controller, and

a power source connected to the external system controller and the temperature controller,

said feedback sensor communicating the detected temperature to the external system controller and the temperature controller, and said external system controller and said temperature controller configured to control the heating element and the cooling element.

The thermal energy system as in claim 15, wherein the external system controller and the temperature controller are configured to control the heating element and the cooling element based on a detected temperature received from the at least one temperature sensor and/or based on user inputs.

The thermal energy system as in claim 15 wherein the heating element and/or the cooling element are connected to the external system controller by a percutaneous wire.

The thermal energy system as in claim 15 wherein the heating element is heated by heated fluid and/or the cooling element is cooled by cooled fluid received through a percutaneous tube from at least one fluid reservoir communicating fluidly with at least one fluid pump controlled by the external system controller.

The thermal energy system as in claim 15 wherein the system controller receives and processes biological signals of the subject from the at least one feedback sensor. A fully implantable thermal energy system for reversible blockade of a nerve in the body of a subject, said fully implantable thermal energy system comprising

at least one heating element configured to be implanted near the nerve, at least one cooling element configured to be implanted near the nerve, at least one feedback sensor capable of detecting temperature near at least one location,

a temperature controller and a system controller connected to a power source and configured to control the heating element and the cooling element.

The thermal energy system as in claim 20, wherein the system controller and the temperature controller are configured to control the heating element and the cooling element based on a detected temperature received from the at least one temperature sensor and/or based on user inputs.