Temperature-adjustable method for cooling dorsal root ganglion and easing pain

Abstract

The invention discloses a temperature-adjustable analgesic method for cooling dorsal root ganglion, which is characterized in that according to the characteristics of complicated anatomical structure and extremely small size of the dorsal root ganglion, a miniature thermoelectric refrigeration device which is small in size, capable of being embedded in vivo, high in biocompatibility, wide in refrigeration range and capable of being stably fixed is designed. Meanwhile, the device has the characteristics of capability of quantitatively regulating and controlling the refrigerating temperature, no external refrigerating cycle, low cost and the like; besides, under the condition that the nerve structure is not damaged, the device can effectively slow down inherent nerve activity and inhibit abnormal discharge of neurons, so that the device is used for gently cooling and regulating DRG to relieve chronic pain. The invention not only opens up a brand-new treatment way for chronic pain patients who have been addicted or tolerated to drugs, but also is expected to be expanded to the field of pain management of animals such as pets and racing horses.

Description

Technical Field

[0001] The invention relates to a temperature-adjustable method for cooling dorsal root ganglia for analgesia. Background Art

[0002] Chronic pain refers to pain that lasts for more than 3 months, mainly seen in traumatic injuries to the peripheral or central nervous system, cardiac or thoracic surgery, cancer or cancer chemotherapy, etc. Its recurring and refractory characteristics make patients suffer for a long time. A recent article published in the Lancet pointed out that chronic pain has brought a huge burden to individuals and the economy, affecting more than 30% of the world's population. The "China Pain Medicine Development Report (2020)" pointed out that there are more than 300 million chronic pain patients in my country, and it is growing at a rate of 10 to 20 million per year. It has become the third largest health problem after cardiovascular and cerebrovascular diseases and tumors. In recent years, although the research on the mechanism of chronic pain has made great progress, clinical treatment still faces huge challenges, especially for chronic pain patients who have become addicted or tolerant to drugs.

[0003] Dorsal root ganglion (DRG) is the location of the first-order neurons that transmit somatic pain. Due to the special role of DRG in the modulation, amplification and filtering of pain signals, various treatment methods for DRG, such as chemical drug blockade, pulsed radiofrequency, and electrical stimulation, have been used in the treatment of chronic pain in recent years. However, the effects of the above analgesic methods are unstable and the mechanism of action is unclear, which seriously affects their clinical promotion and application.

[0004] Mild local cooling has been shown to effectively slow intrinsic neural activity and inhibit abnormal neuronal discharge without damaging neural structures. Therefore, cooling the DRG is a promising method to block pain signals because it is non-addictive, rapidly reversible, can be applied locally, and avoids any pathological reactions. However, due to the complex anatomical structure of the DRG, the small size of the intervertebral foramen, the difficulty of device fixation, and the biosafety of the cooling device, there is currently no suitable micro-refrigeration device for DRG cooling analgesia. Current neural cooling methods rely on rigid and bulky cooling systems, making local cooling an impractical method for treating neural pain. In addition, due to the complexity of the DRG anatomical structure, no device for relieving pain by cooling the DRG has been reported. Summary of the invention

[0005] In view of the deficiencies in the prior art, the purpose of the present invention is to provide a method for cooling dorsal root ganglia for analgesia with adjustable temperature. According to the complex anatomical structure and extremely small size of DRG, an innovative miniature thermoelectric cooling device with small size, implantable in vivo, high biocompatibility, wide cooling range and stable fixation is designed. At the same time, the device has the characteristics of quantitatively controlling the cooling temperature, no external refrigeration cycle and low cost, and can be used to gently cool and control DRG to relieve chronic pain.

[0006] In order to solve the above technical problems, the present invention adopts the following technical solutions to achieve the above problems:

[0007] A method for cooling dorsal root ganglion with adjustable temperature for analgesia, comprising the following steps:

[0008] S1. Implant the micro thermoelectric cooling device into the dorsal root ganglion and deploy a control temperature regulation module and a fixing strap;

[0009] S2. The micro thermoelectric cooling device is powered on and starts cooling;

[0010] S3. Cooling of dorsal root ganglia by micro thermoelectric cooling device;

[0011] S4. Nerve activity slows down, abnormal discharge of neurons is inhibited, and pain signal transmission is blocked;

[0012] S5. If the pain is relieved, the process ends; otherwise, the required cooling temperature instruction is adjusted and issued, the temperature regulating module is controlled to adjust the input current, and steps S2 to S5 are repeated.

[0013] The present invention also includes the following technical features:

[0014] Specifically, the S1 includes:

[0015] The micro thermoelectric cooling device is surgically implanted into the intervertebral foramen and fixed to the spine, while ensuring that the cooling probe on the micro thermoelectric cooling device is close to the dorsal root ganglion to achieve cooling function;

[0016] The control temperature adjustment module is connected to the micro thermoelectric refrigeration device through the power supply wire and the temperature sensing wire respectively to realize the power supply and temperature adjustment functions;

[0017] The fixing strap is connected to the control temperature regulation module to achieve stable fixation around the waist.

[0018] Specifically, in the micro-thermoelectric cooling device, the hot surface of the thermoelectric cooler is connected to the inner side of one end of the clip-type thermal conductive copper sheet, the outer side of the thermal conductive copper sheet is connected to the columnar heat dissipation copper sheet, and the cold surface of the thermoelectric cooler is connected to a cooling probe with the needle tip exposed. A micro-thermocouple temperature probe is mounted on the needle tip for real-time temperature monitoring; the cooling probe has a diameter of 0.4 mm and a length of 2 mm.

[0019] Specifically, the thickness of the thermoelectric cooler is 1.6±0.1 mm, the resistance is 2.4-2.6Ω, and the temperature difference ΔTmax between the hot end and the cold end of the thermoelectric cooler is 125°C.

[0020] Specifically, the thermoelectric cooler is under load Q c =0W, hot end temperature Th = 85°C, the relationship between the temperature difference between the cold end and the hot end of the thermoelectric cooler and the current is:

[0021] ΔT = 272.01×I-238.53×I 2 +114.54×I 3 -26.51×I 4 +0.3 (1)

[0022] Where: I is the input current of the thermoelectric cooler, unit is A; ΔT is the temperature difference between the hot end and the cold end of the thermoelectric cooler, unit is ℃.

[0023] Specifically, the heat exchange relationship between the thermoelectric cooler and the biological tissue is:

[0024]

[0025] Where: t is the biological tissue density, unit: kg·m -3 ;c t is the heat capacity of biological tissue, unit J·kg -1 ·K -1 ; T is tissue temperature, unit K; t is time, unit s; k t is the thermal conductivity of the tissue, in W·m -1 ·K -1 ;ω b is the blood perfusion rate, in kg·m -3 ·s -1 ;c b is the specific heat of blood, unit J·kg -1 ·K -1 ; T a is the arterial blood temperature, unit K; T v is the venous blood temperature, unit K; Q met is the heat produced by tissue metabolism, unit: W·m -3 ;Q s is the heat exchanged between the thermoelectric cooler and the biological tissue, in W·m -3 .

[0026] Specifically, the heat exchange amount Q between the thermoelectric cooler and the external environment is h :

[0027]

[0028] Where: Q h is the heat exchange capacity, unit J; h is the convection heat transfer coefficient between the thermoelectric cooler and the environment, unit W·m -2 ·K -1 ; A is the heat exchange surface area between the thermoelectric cooler and the environment, unit: m 2 ; T e is the temperature of the thermoelectric cooler, in K; T k is the ambient temperature, unit K; t is the time, unit s.

[0029] Specifically, the control temperature adjustment module includes a temperature sensor, a microcontroller, a refrigeration drive circuit, and a human-computer interaction interface;

[0030] A temperature sensor for measuring the actual temperature of the micro-thermoelectric cooling device;

[0031] A microcontroller is used to receive the signal from the temperature sensor and output a corresponding control signal;

[0032] A refrigeration drive circuit, used to control the input current of the micro-thermoelectric refrigeration device and adjust the working state of the micro-thermoelectric refrigeration device according to the control signal output by the microcontroller;

[0033] The human-computer interaction interface is used to enable the user to set the target temperature and view the current temperature information through buttons, touch screens, and remote communication.

[0034] Specifically, the temperature control module temperature control process: the user sets the target temperature through the human-computer interaction interface; the microcontroller receives the target temperature and obtains the current temperature information from the temperature sensor; the microcontroller calculates the control signal according to the preset PID control algorithm, and outputs the control signal to the refrigeration drive circuit; the refrigeration drive circuit adjusts the input current of the micro-thermoelectric refrigeration device according to the control signal, and changes the refrigeration capacity of the refrigeration device; the temperature sensor continuously monitors the temperature change of the micro-thermoelectric refrigeration device and feeds back the signal to the microcontroller; the microcontroller continuously adjusts the control signal according to the feedback signal and the target temperature until it reaches and maintains within the target temperature range.

[0035] Specifically, the PID control algorithm calculation formula is:

[0036] u(t) = K p ×[e(t) + 1 / T i ×∫e(t)dt + T d ×de(t) / dt] (4)

[0037] In the formula, u(t) represents the control quantity of the PID control algorithm at time t, K pis the proportionality coefficient, T i is the integration time constant, T d is the differential time constant, e(t) is the feedback error, and t is the time; by adjusting K p , T i , T d The three coefficients can control the stability, accuracy and response speed of the system to achieve good control effect.

[0038] Compared with the prior art, the present invention has the following technical effects:

[0039] The micro thermoelectric cooling device designed by the present invention can be implanted in the dorsal root ganglion in vivo, and is suitable for cooling and regulating the dorsal root ganglion. The results of in vivo mouse temperature tests showed that the micro thermoelectric cooling device can cool the dorsal root ganglion to below 25°C, and the hot end temperature does not exceed 40°C. Mild local cooling has been shown to effectively slow down intrinsic neural activity without damaging neural structures. Therefore, the micro thermoelectric cooling device is expected to play an analgesic role by cooling the dorsal root ganglion and slowing down the electrophysiological activity of the pain signal transmission nerves. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 Schematic diagram of cooling the dorsal root ganglion for analgesia.

[0041] Figure 2 Flow chart of the principle of analgesia by cooling the dorsal root ganglion.

[0042] Figure 3 A schematic diagram of the system.

[0043] Figure 4 Schematic diagram of TEC structure dimensions.

[0044] Figure 5 A micro thermoelectric refrigeration device for cooling dorsal root ganglia for analgesia: A is a schematic diagram of the components, and B is a schematic diagram of the entire device after assembly.

[0045] Figure 6 This is the relationship curve between the cooling temperature difference and the current when the hot end temperature Th of the thermoelectric cooler is 85℃ and the load Qc is 0W.

[0046] Figure 7 Flow chart for controlling temperature regulation.

[0047] Figure 8 Flow chart of the experiment to test the pain relief effect of cooling DRG based on a micro-thermoelectric cooling device.

[0048] Fig. 9 Temperature curve of mouse DRG cooled by a micro-thermoelectric cooling device with a power of 0.124W.

[0049] Fig.10Temperature curve of mouse DRG cooled by a micro-thermoelectric cooling device with a power of 0.176 W.

[0050] Fig.11 Temperature curve of mouse DRG cooled by a 0.273W micro-thermoelectric cooling device. DETAILED DESCRIPTION

[0051] The present invention provides a method for cooling dorsal root ganglion analgesia with adjustable temperature. According to the characteristics of DRG anatomical structure being complex and extremely small in size, the present invention innovatively designs a micro thermoelectric refrigeration device with small volume, body embedment, high biocompatibility, wide cooling range and stable fixation. At the same time, the device has the characteristics of quantitatively regulating the cooling temperature, no external refrigeration cycle and low cost. In addition, the device can be used to gently cool and regulate DRG to achieve chronic pain relief. The key technologies of the present invention mainly include: (1) DRG is the location of the first-order neurons for somatic pain sensory input, and plays a special role in the modulation, amplification and filtering of pain signals, and is an ideal location for targeted analgesia; (2) DRG has a complex structure and extremely small in size. The refrigeration device of the present invention has a small volume, body embedment, high biocompatibility, wide cooling range and stable fixation, and is suitable for DRG implantation; (3) The refrigeration device of the present invention can quantitatively regulate the cooling temperature, no external refrigeration cycle and low cost; (4) The refrigeration device of the present invention can effectively slow down the inherent neural activity and inhibit the abnormal discharge of neurons without damaging the neural structure.

[0052] Based on the Peltier effect, thermoelectric coolers can transfer electricity into temperature differences. As a green, environmentally friendly, safe and reliable cooling method, thermoelectric cooling is widely used in the fields of heat dissipation and cooling of optical systems, aerospace electronic devices and medical instruments due to its easy packaging, pollution-free, no moving parts and precise temperature control. In particular, TEC can not only be as small as millimeter level, which is convenient for packaging and integration, but also has high cooling heat flux density. It has great application potential in local cooling and microsystem solid-state cooling, and also provides a feasible solution for cooling and regulating DRG analgesia.

[0053] The thermostatic method of the present invention for cooling dorsal root ganglion analgesia, such as Figures 1 to 3 , including the following steps:

[0054] S1. Implantation of a micro thermoelectric cooling device into the dorsal root ganglion;

[0055] Specifically, the micro-thermoelectric cooling device is surgically implanted into the intervertebral foramen and fixed to the spine with screws and dental cement, while ensuring that the cooling probe on the micro-thermoelectric cooling device is close to the dorsal root ganglion to achieve the cooling function; the control temperature regulation module is connected to the micro-thermoelectric cooling device through the power supply wire and the temperature sensor wire respectively to achieve power supply and temperature regulation functions; the fixing strap is connected to the control temperature regulation module to achieve stable fixation around the waist.

[0056] S2. The micro thermoelectric cooling device is powered on and starts cooling;

[0057] S3. Cooling of dorsal root ganglia by micro thermoelectric cooling device;

[0058] S4. Nerve activity slows down, abnormal discharge of neurons is inhibited, and pain signal transmission is blocked;

[0059] S5. If the pain is relieved, the process ends; otherwise, the required cooling temperature instruction is adjusted and issued, the temperature regulating module is controlled to adjust the input current, and steps S2 to S5 are repeated.

[0060] Thermoelectric coolers (TEC) use the Peltier effect. When current passes through a circuit containing two different conductors or semiconductors, a temperature change occurs near the junction, one of which absorbs heat and the other releases heat, thereby forming cooling. Thermoelectric coolers have the advantages of small size, light weight, and low noise, and have been widely used in the biomedical field. The size of the thermoelectric cooler TEC structure used in the present invention is as follows: Figure 4 The key parameters are shown in Table 1.

[0061] Table 1 TEC key parameters

[0062]

[0063] The present invention uses a thermoelectric cooler (TEC) as a basic cooling unit. In order to be suitable for cooling DRG implanted in mice, the present invention has specially designed the TEC, such as Figure 5 As shown. The hot surface of the TEC is connected to the inner side of one end of the clip-type thermal conductive copper sheet, and the outer side of the thermal conductive copper sheet is connected to the columnar heat dissipation copper sheet. The cold surface of the TEC is connected to a cooling probe with a diameter of 0.4mm and a length of 2mm. The needle tip is exposed, and the rest of the part is covered with a thermal insulation sleeve. A miniature thermocouple temperature probe is also installed on the needle tip for real-time temperature monitoring.

[0064] Thermoelectric cooler load Q c = 0W, hot end temperature Th = 85°C, the relationship between the temperature difference between the cold end and the hot end of the thermoelectric cooler and the current is as follows Figure 6 As shown. Through fitting, the relationship between the two can be described by formula (1):

[0065] ΔT = 272.01×I-238.53×I 2 +114.54×I 3 -26.51×I 4 +0.3 (1)

[0066] Where: I is the input current of the thermoelectric cooler, unit is A; ΔT is the temperature difference between the hot end and the cold end of the thermoelectric cooler, unit is ℃.

[0067] Under actual working conditions, there is heat exchange between the refrigeration device and the biological tissue and the external environment. The total load of the refrigeration device is Q c Affected by these processes. The heat exchange process between the thermoelectric cooler of the refrigeration device and the biological tissue can be described by formula 2:

[0068]

[0069] Where: t is the biological tissue density, unit: kg·m -3 ;c t is the heat capacity of biological tissue, unit J·kg -1 ·K -1 ; T is tissue temperature, unit K; t is time, unit s; k t is the thermal conductivity of the tissue, in W·m -1 ·K -1 ;ω b is the blood perfusion rate, in kg·m -3 ·s -1 ;c b is the specific heat of blood, unit J·kg -1 ·K -1 ; T a is the arterial blood temperature, unit K; T v is the venous blood temperature, unit K; Q met is the heat produced by tissue metabolism, unit: W·m -3 ;Q s The heat exchanged between the thermoelectric cooler of the refrigeration device and the biological tissue, in W·m -3 .

[0070] The heat exchange amount Q between the thermoelectric cooler of the refrigeration device and the external environment h It can be described by formula 3:

[0071]

[0072] Where: Q h is the heat exchange amount, unit J; h is the convection heat transfer coefficient between the thermoelectric cooler of the refrigeration device and the environment, unit W·m -2 ·K -1; A is the heat exchange surface area between the thermoelectric cooler of the refrigeration device and the environment, unit m 2 ; T e is the temperature of the thermoelectric cooler of the refrigeration device, unit K; T k is the ambient temperature, unit K; t is the time, unit s.

[0073] Control temperature adjustment module: according to the pain perception, issue the required cooling temperature command. The circuit principle of the micro thermoelectric cooling device to adjust the temperature through the command includes components such as temperature sensor, controller and actuator.

[0074] The control temperature adjustment module includes a temperature sensor, a microcontroller, a refrigeration drive circuit, and a human-computer interaction interface; the temperature sensor's temperature probe is fixed to the tip of a cooling probe of a micro-thermoelectric refrigeration device, and the temperature probe is connected to a thermocouple circuit via a temperature measuring wire, and the circuit is arranged in the control temperature adjustment module.

[0075] The following is a brief description of the circuit principle of the refrigeration system temperature control through command:

[0076] 1) Temperature sensor: A thermocouple circuit and temperature sensor used to measure the actual temperature of the refrigeration unit.

[0077] 2) Microcontroller (MCU): Receives the signal from the temperature sensor and outputs the corresponding control signal according to the preset temperature range and control algorithm.

[0078] 3) Refrigeration drive circuit: According to the control signal output by the microcontroller, the input current of the micro thermoelectric refrigeration device is controlled to adjust the working state of the refrigeration device.

[0079] 4) Human-computer interaction interface: Through buttons, touch screens, remote communications, etc., users can set target temperature, view current temperature and other information.

[0080] like Figure 7 As shown in the figure, the temperature adjustment process in actual use is as follows: the user sets the target temperature through the human-computer interaction interface. The microcontroller receives the target temperature and obtains the current temperature information from the temperature sensor. The microcontroller calculates the control signal according to the preset PID control algorithm or the improved PID control algorithm and outputs it to the refrigeration drive circuit. The refrigeration drive circuit adjusts the input current of the micro-thermoelectric refrigeration device according to the control signal to change the refrigeration capacity of the refrigeration device. The temperature sensor continuously monitors the temperature change of the micro-thermoelectric refrigeration device and feeds back the signal to the microcontroller. The microcontroller continuously adjusts the control signal according to the feedback signal and the target temperature until it reaches and maintains within the target temperature range. Through this closed-loop control method, the micro-thermoelectric refrigeration device can automatically adjust and maintain within the set temperature range according to the instructions.

[0081] For example, the current input current is 0.15A, the cold end temperature is 28℃, and the user inputs the expected temperature of 26℃ as needed. The microcontroller calculates the control signal through the PID control algorithm and adjusts the input current of the drive circuit (assuming it is 0.2A). The cooling capacity of the refrigeration module increases, and the temperature sensor collects the temperature and compares it with the input expected temperature of 26℃. If there is a deviation, the deviation value is returned to the microcontroller and the above process is repeated until the refrigeration temperature measurement value has no deviation from the input expected temperature, thus achieving temperature control.

[0082] The PID control algorithm can be described by Equation 4:

[0083] u(t) = K p ×[e(t) + 1 / T i ×∫e(t)dt + T d ×de(t) / dt] (4)

[0084] In the formula, u(t) represents the control quantity of the PID control algorithm at time t, K p is the proportionality coefficient, T i is the integration time constant, T d is the differential time constant, e(t) is the feedback error, and t is the time. p , T i , T d The three coefficients can control the stability, accuracy and response speed of the system to achieve better control effects.

[0085] Specific embodiments of the present invention are given below. It should be noted that the present invention is not limited to the following specific embodiments, and all equivalent changes made on the basis of the technical solution of this application fall within the protection scope of the present invention.

[0086] Example:

[0087] This example provides an experimental process for testing the cooling effect of in vivo cooling of mouse dorsal root ganglia, including:

[0088] 1. Experimental animals: C57BL / 6 mice, kept in an environment with a temperature of 25°C, a humidity of 35-45%, and lighting that simulates a 12-hour day-night cycle. The animals were free to move and eat in isolation cages, and adequate food and water were provided.

[0089] 2. Implantation of a micro thermoelectric cooling device into mouse DRG: Mice were anesthetized with 2% isoflurane / oxygen, while the body temperature was maintained at 36.5°C. A dorsal incision was made on the outside of the intervertebral foramen at the level of the fourth lumbar (L4) spinal nerve to expose the intervertebral foramen, and the accessory processes hanging from the intervertebral foramen were removed. A probe with a diameter of 0.4 mm was inserted into the intervertebral foramen on the outside of the DRG (located in the middle part of the dorsal and ventral sides of the DRG) to create a space, and the cold end probe of the cooling device was inserted into a position close to the DRG to achieve direct cooling of the DRG. The clip-type thermal conductive copper sheet spans both sides of the spine and is fixed with dental cement. The wires pass through the tunnel to the head, and the connecting hub is fixed to the skull using dental cement and screws.

[0090] 3. In vivo temperature measurement experiment of cooling DRG: The temperature measuring thermocouples are arranged at the tip of the cooling probe, the surface of the heat dissipation copper sheet connected to the hot surface of the micro-thermoelectric cooling device, and the mouse cage. After the micro-thermoelectric cooling device is implanted in the mouse DRG, the initial temperature is first collected for 5 minutes, and then the cooling DRG temperature, hot end temperature and ambient temperature are synchronously recorded by providing different power supplies.

[0091] This example provides a test scheme for the pain relief effect of SNI by cooling DRG with a micro thermoelectric refrigeration device:

[0092] The experiment established a preserved nerve injury (SNI) mouse model, implanted a micro-thermoelectric cooling device to cool the DRG as a treatment method, and evaluated the pain relief of SNI mice by cooling the DRG at different temperatures through behavioral experiments such as mechanical hyperalgesia paw withdrawal threshold (PWT) and cold pain (acetone), to clarify the therapeutic effect of micro-thermoelectric cooling device implanted in local DRG cooling technology on chronic pain. The test experimental process is as follows Figure 8 shown.

[0093] 1. Sparing nerve injury (SNI) mouse model: The classic chronic pain SNI model was used as the experimental model. The lateral surface of the thigh was incised and the biceps femoris was cut to expose the sciatic nerve and its three terminal branches: the sural nerve, the common peroneal nerve, and the tibial nerve. The tibial nerve and the common peroneal nerve were cut and tightly ligated with 6-0 silk thread, while the sural nerve was retained to form a preserved nerve injury. The common peroneal nerve and the tibial nerve were sliced ​​at the distal end of the ligation, and 2-4 mm of the distal nerve stump was removed to prevent nerve regeneration. Care was taken to avoid contact or stretching the intact sural nerve. The muscles and fascia were sutured in layers, and the skin was sutured with a stapler.

[0094] 2. Paw Withdrawal Threshold (PWT) for Mechanical Hyperalgesia: The test was performed using calibrated von Frey filaments. Briefly, starting with a 2.8 g filament, the tip of the filament was held perpendicular to the hairless skin on the lateral third of the hind paw for 1 second with just enough force to bend the filament. If a paw withdrawal response was observed, the next weaker filament was applied, and if no response was observed, the next harder filament was applied until a reversal occurred. After a reversal event, four more stimulations were performed following the same pattern with at least 10 seconds between stimulations. The forces of the filaments applied before and after the reversal, as well as the forces of the four filaments applied after the reversal, were used to calculate the 50% withdrawal threshold. Mice that did not respond to any of the filaments were assigned a score of 25 g. In the absence of a hypersensitive state, animals tended to default to a score of 25 g.

[0095] 3. Cold allodynia (acetone): Sensitivity to cold is assessed using acetone, which is sprayed vertically through a tube that forms a raised meniscus at the end of the tube. The tube is touched to the plantar skin without the tube touching the skin. If the paw moves, the reaction is positive. Repeat 3 times with at least 1 minute between each application. The method for quantifying sensitivity to acetone is to tabulate the number of reactions as a percentage of the total number of applications. Animals that are allergic to acetone rarely react.

[0096] According to the experimental results of cooling the dorsal root ganglion of mice in vivo, Fig. 9 As shown in Figure 1, when the room temperature is about 22°C and the power supply is 0.124W, the temperature of the micro thermoelectric cooling device does not exceed 34.8°C, and the dorsal root ganglion can be cooled to 25.1°C; Fig.10 As shown in Figure 1, when the room temperature is about 22°C and the power supply is 0.176W, the temperature of the micro thermoelectric cooling device does not exceed 36.8°C, and the dorsal root ganglion can be cooled to 24.7°C; Fig.11 As shown, when the room temperature is about 22°C and the power supply is 0.273W, the temperature of the micro thermoelectric cooling device does not exceed 39.4°C and the dorsal root ganglion can be cooled to 24.5°C.

[0097] The preferred embodiments of the present invention are described in detail above in conjunction with the accompanying drawings. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, a variety of simple modifications can be made to the technical solution of the present invention, and these simple modifications all belong to the protection scope of the present invention.

[0098] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not further describe various possible combinations.

[0099] In addition, various embodiments of the present invention may be arbitrarily combined, and as long as they do not violate the concept of the present invention, they should also be regarded as the contents disclosed by the present invention.

Claims

1. A thermostatic method for cooling dorsal root ganglion analgesia, characterized in that: The following steps are involved: S1. Implant the micro thermoelectric cooling device into the dorsal root ganglion and deploy a control temperature regulation module and a fixing strap; S2. The micro thermoelectric cooling device is powered on and starts cooling; S3. Cooling of dorsal root ganglia by micro thermoelectric cooling device; S4. Nerve activity slows down, abnormal discharge of neurons is inhibited, and pain signal transmission is blocked; S5. If the pain is relieved, the process ends; otherwise, the required cooling temperature instruction is adjusted and issued, the temperature regulating module is controlled to adjust the input current, and steps S2 to S5 are repeated.

2. The thermostatic method for cooling dorsal root ganglion analgesia according to claim 1, characterized in that: The S1 includes: The micro thermoelectric cooling device is surgically implanted into the intervertebral foramen and fixed to the spine, while ensuring that the cooling probe on the micro thermoelectric cooling device is close to the dorsal root ganglion to achieve cooling function; The control temperature adjustment module is connected to the micro thermoelectric refrigeration device through the power supply wire and the temperature sensing wire respectively to realize the power supply and temperature adjustment functions; The fixing strap is connected to the control temperature regulation module to achieve stable fixation around the waist.

3. The thermostatic method for cooling dorsal root ganglion analgesia according to claim 1, characterized in that: In the micro thermoelectric cooling device, the hot surface of the thermoelectric cooler is connected to the inner side of one end of a clip-type heat-conducting copper sheet, the outer side of the heat-conducting copper sheet is connected to a columnar heat-dissipating copper sheet, and the cold surface of the thermoelectric cooler is connected to a cooling probe with the needle tip exposed. A micro thermocouple temperature probe is mounted on the needle tip for real-time temperature monitoring; the cooling probe has a diameter of 0.4 mm and a length of 2 mm.

4. The thermostatic method for cooling dorsal root ganglion analgesia according to claim 3, characterized in that: The thickness of the thermoelectric cooler is 1.6±0.1 mm, the resistance is 2.4-2.6Ω, and the temperature difference ΔTmax between the hot end and the cold end of the thermoelectric cooler is 125°C.

5. The thermostatic method for cooling dorsal root ganglion analgesia according to claim 3, characterized in that: The thermoelectric cooler is under load Q c =0W, hot end temperature Th = 85°C, the relationship between the temperature difference between the cold end and the hot end of the thermoelectric cooler and the current is: ΔT = 272.01×I-238.53×I 2 +114.54×I 3 -26.51×I 4 +0.3 (1) Where: I is the input current of the thermoelectric cooler, unit A; ΔT is the temperature difference between the hot end and the cold end of the thermoelectric cooler, in °C.

6. The thermostatic method for cooling dorsal root ganglion analgesia according to claim 3, characterized in that: The heat exchange relationship between the thermoelectric cooler and the biological tissue is: Where: t is the biological tissue density, unit: kg·m -3 ;c t is the heat capacity of biological tissue, unit J·kg -1 ·K -1 ; T is tissue temperature, unit K; t is time, unit s; k t is the thermal conductivity of the tissue, in W·m -1 ·K -1 ;ω b is the blood perfusion rate, in kg·m -3 ·s -1 ;c b is the specific heat of blood, unit J·kg -1 ·K -1 ; T a is the arterial blood temperature, unit K; T v is the venous blood temperature, unit K; Q met is the heat produced by tissue metabolism, unit: W·m -3 ;Q s is the heat exchanged between the thermoelectric cooler and the biological tissue, in W·m -3 .

7. The thermostatic method for cooling dorsal root ganglion analgesia according to claim 3, characterized in that: The heat exchange amount Q between the thermoelectric cooler and the external environment h : Q h =|hA(T e -T k )dt (3) Where: Q h is the heat exchange capacity, unit J; h is the convection heat transfer coefficient between the thermoelectric cooler and the environment, unit W·m -2 ·K -1 ; A is the heat exchange surface area between the thermoelectric cooler and the environment, unit: m 2 ; T e is the temperature of the thermoelectric cooler, in K; T k is the ambient temperature, unit K; t is the time, unit s.

8. The thermostatic method for cooling dorsal root ganglion analgesia according to claim 1, characterized in that: The control temperature adjustment module includes a temperature sensor, a microcontroller, a refrigeration drive circuit, and a human-computer interaction interface; A temperature sensor for measuring the actual temperature of the micro-thermoelectric cooling device; A microcontroller is used to receive the signal from the temperature sensor and output a corresponding control signal; A refrigeration drive circuit, used to control the input current of the micro-thermoelectric refrigeration device and adjust the working state of the micro-thermoelectric refrigeration device according to the control signal output by the microcontroller; The human-computer interaction interface is used to enable the user to set the target temperature and view the current temperature information through buttons, touch screens, and remote communication.

9. The thermostatic method for cooling dorsal root ganglion analgesia according to claim 8, characterized in that: The temperature control module temperature adjustment process: the user sets the target temperature through the human-computer interaction interface; the microcontroller receives the target temperature and obtains the current temperature information from the temperature sensor; the microcontroller calculates the control signal according to the preset PID control algorithm and outputs the control signal to the refrigeration drive circuit; The refrigeration drive circuit adjusts the input current of the micro-thermoelectric refrigeration device according to the control signal, thereby changing the refrigeration capacity of the refrigeration device; the temperature sensor continuously monitors the temperature changes of the micro-thermoelectric refrigeration device and feeds back the signal to the microcontroller; the microcontroller continuously adjusts the control signal according to the feedback signal and the target temperature until the target temperature range is reached and maintained.

10. The thermostatic method for cooling dorsal root ganglion analgesia according to claim 9, characterized in that: The PID control algorithm calculation formula: u(t) = K p ×[e(t) + 1 / T i ×∫e(t)dt + T d ×de(t) / dt] (4) In the formula, u(t) represents the control quantity of the PID control algorithm at time t, K p is the proportionality coefficient, T i is the integration time constant, T d is the differential time constant, e(t) is the feedback error, and t is the time; by adjusting K p , T i , T d The three coefficients can control the stability, accuracy and response speed of the system to achieve good control effect.

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