CN117919592A - Use of electrical stimulation in tissue damage - Google Patents
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- CN117919592A CN117919592A CN202211252762.1A CN202211252762A CN117919592A CN 117919592 A CN117919592 A CN 117919592A CN 202211252762 A CN202211252762 A CN 202211252762A CN 117919592 A CN117919592 A CN 117919592A
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Abstract
The invention provides an electric stimulation treatment mode with high targeting property, strong specificity and smaller wound, which is mainly used for tissue injury and relieving tendon adhesion; through local stimulation of skin, nerve tissue such as sympathetic nerve at damaged tissue is further electrically stimulated, so that sympathetic nerve is promoted to release anti-inflammatory factors, and pro-inflammatory factors at the damaged tissue are reduced, thereby relieving the damage of the tissue, reducing the occurrence rate of tendon adhesion at the damaged tissue and promoting healing.
Description
Technical Field
The present invention relates to the field of biomedical and medical technology. And in particular to the relevant application of electrical stimulation in tissue damage.
Background
Electrical stimulation is an experimental method and therapeutic approach widely used in basic research and clinical practice. In basic research, it has a complex and extensive impact on ex vivo levels of cells, tissues, organs. Meanwhile, skeletal muscles, smooth muscles and the like are affected to different degrees, and especially, the effects that other internal medicine treatments or surgical treatments cannot be replaced are achieved in the treatment of nervous system diseases and mental diseases. Such as dystonia, epilepsy, obsessive-compulsive disorder (OCD), parkinson's Disease (PD), and other movement disorders. For the central nervous system diseases, deep Brain Stimulation (DBS) is mostly used clinically, that is, electrodes are implanted into corresponding brain nuclei and set to specific frequencies, and after continuous or intermittent stimulation for a period of time, the deep brain stimulation has obvious help to control disease symptoms and improve life quality of patients.
The damaged local tissues are changed in cell degeneration, metabolism abnormality and the like after the tissues are damaged, further, due to tissue inflammatory reaction, fibroblast cells are induced to be recruited to a damaged area and proliferated in a large quantity, extracellular matrixes such as collagen fibers and the like are generated, and the extracellular matrixes invade a damaged part to finish exogenous repair, and adhesion is formed. In the case of tendon injury, since inflammatory reaction can lead exogenous healing to cause tendon adhesion, how to reduce the extent of tendon adhesion after injury repair, ensure tendon healing itself and recover functions as soon as possible, and become the focus of research in recent years, drugs for inhibiting inflammatory reaction or inhibiting cytokine release are often clinically used to prevent adhesion. On the one hand, traditional treatment methods such as hormone medicines, manual treatment, external application medicines, traditional Chinese medicine combination manual treatment, acupoint sealing treatment and the like inhibit local vasodilation, enhance vascular tension, reduce congestion, reduce vascular permeability, inhibit adhesion and contracture caused by inflammation, and especially hormones such as Glucocorticoids (GC) and hyaluronidase (hyaluronidase, HAas) are beginning to be applied to soft tissue injury pain treatment, so that the medicine diffusion can be better promoted, the adhesion can be eliminated, the pain can be relieved and the recovery of soft tissue injury can be promoted. The tissue at the damaged part can be naturally repaired and healed, but the repair of the tissue is represented by the regeneration of the tissue and is realized by cell actions such as migration, differentiation, proliferation, matrix secretion and the like of cells, and the cell actions are related to chemical signals transmitted by information among cells, electric signals released by neurotransmitters and the like. The electrical stimulation therapy can accelerate tissue repair by establishing a nerve interface, maintaining or applying proper microcurrent stimulation, and achieve the aim of healing. Research shows that the low-frequency current directly acts on the diseased part or corresponding acupuncture points of the human body to excite the neuromuscular, thereby promoting the muscle to relax or contract and further recovering the exercise function; by dilating blood vessel, promoting local blood circulation of affected part, and improving muscle function.
At present, the electric stimulation is widely applied to clinical and laboratory researches, and people utilize the electric stimulation to achieve proliferation of nerve synapses, regulate differentiation, stimulate cerebral cortex, treat damaged skin, establish regeneration model cell growth of specific tissues in amputation of limbs and stumps of rats and the like. The application of the electric stimulation treatment in biology, such as patent 201210232655.2 reports the application of a hand-held portable percutaneous nerve electric stimulation pain relieving method and a pain relieving device, mainly achieving physiotherapy pain relieving effect through electric stimulation; 201010593161.8 discloses an inductive electric stimulator for promoting nerve regeneration, which stimulates damaged nerves or acupoints through stimulating electrodes, thereby promoting nerve regeneration. The electrical stimulation treatment mainly acts on the nervous system, the tissue range area for treatment is wider, direct intervention is avoided, the targeting is poor, and the specificity is not high; at the same time, the electrodes are not directly placed on the nerves, and besides the effect on the nerves, the electric stimulation has the side effect of electric burn on tissues around the electrodes.
Research shows that the sympathetic nerves are involved in a plurality of human pathophysiological processes such as emotion, inflammation, vasoconstriction, gland secretion and the like through neurotransmitter release, and are one of important targets for clinical treatment. Currently, the regulation of sympathetic neurotransmitters is mainly pharmaceutical, and physical therapy is very limited. Animal models are important tools for researching the interaction, and researchers try to directly interfere with the interaction release transmitter by using an electric stimulation mode on a mouse model so as to interfere with local inflammation, reduce cytokines such as TNF-alpha, IL-6 and the like, reduce and prevent tendon adhesion after injury repair, and recover functions as soon as possible. Therefore, development of an electrical stimulation technology which is high in targeting property, high in specificity and convenient for clinical application is needed.
Disclosure of Invention
In order to solve the problems, the invention provides an electrical stimulation treatment mode which can be specifically interfered and has small wound, and the electrical stimulation treatment mode is mainly used for treating tissue injury and relieving inflammatory response caused by the tissue injury.
In a first aspect, the invention provides a use of electrical stimulation in the manufacture of an apparatus for treating tissue damage, the use comprising reducing inflammation and/or tissue adhesion prevention caused by the tissue damage.
Further, the tissue injury refers to mechanical injury of soft tissues such as ligaments, articular cartilage, skeletal muscle and the like, and inflammatory reaction caused by the injury. The inflammatory reaction of the tissue has a great deal of proliferation of fibroblasts, collagen fibers are generated, the collagen fibers invade the damaged part to finish exogenous repair, adhesion is formed, local adhesion can form pain points, and pain is finally caused.
Further, the inflammation is caused by inflammatory factors such as interleukin (interleukin, IL), interferon (IFN), and tumor necrosis factor (tumornecrosisfactor, TNF). Preferably, the inflammatory factor is selected from TNF-alpha and/or IL-6.
Further, the electrical stimulation refers to electrical stimulation of nerve tissue such as sympathetic nerve tissue at damaged tissue, and the electrical stimulation parameters are as follows: 0.3-3 mA, 10-50 Hz, and the duration of the stimulus is 5-20 minutes. Preferably, the electrical stimulation is performed in a percutaneous electrical stimulation and a regulatable implantable electrical stimulation.
In a second aspect, the present invention provides an electrical stimulation therapy apparatus comprising a power source, a memory, an electrode and a connecting wire thereof, wherein the electrode is sheet-shaped or needle-shaped.
In one embodiment, the sheet electrode is applied to the skin surface of damaged tissue, and the nerve tissue such as sympathetic nerve tissue at the damaged tissue is electrically stimulated to reduce inflammatory factors at the affected part, thereby relieving the damage of the tissue, preventing tendon adhesion and promoting healing.
In one embodiment, the sheet electrode is implanted into subcutaneous tissue at the lesion, and the nerve tissue such as sympathetic nerve tissue at the lesion is electrically stimulated to reduce inflammatory factors at the lesion, thereby relieving the damage of the tissue, preventing tendon adhesion, and promoting healing.
In another embodiment, the electrode is a needle electrode, the needle electrode is fixed on a substrate, a plurality of insertion holes of the needle electrode can be formed on the substrate, and the number of the inserted electrodes on the substrate can be determined according to the size of the skin area of the affected part.
The electrical stimulation therapeutic apparatus provided by the invention further stimulates nerve tissues such as sympathetic nerve tissues at the damaged tissues through local skin stimulation, reduces the quantity of inflammatory factors such as TNF-alpha and IL-6, reduces the occurrence rate of tendon adhesion at the damaged tissues, promotes healing, and is a precise therapeutic mode with small wounds and high specificity.
Drawings
FIG. 1 schematic representation of peri-pancreatic implant electrode via the cranium
Figure 2 lateral recumbent blunt dissection until abdominal aorta
FIG. 3 sympathetic nerves between the lumbar and diaphragmatic muscle dead centers
FIG. 4 suture wound
FIG. 5 relationship of sympathetic electrical stimulation and inflammatory factors
Detailed Description
Definition of the definition
The term "for example" should be used as an example, not as a limitation, and should not be construed as referring to only those items explicitly recited in the specification.
The term "transcutaneous electrical stimulation" as used herein is the attachment of an electrode to the skin, the magnitude of the current being controlled by adjusting the voltage and the resistance between the electrode and the skin interface.
The term "implantable electrical stimulation" as used herein is to surgically implant electrodes into the subcutaneous tissue surrounding the sympathetic nerve for stimulating the sympathetic nerve.
The term "transcranial apical electric stimulation" used in the present invention means that the current can stimulate cortical neurons with sinusoidal and biphasic alternating current, and the stimulation position and intensity can be changed according to the treatment requirement, thus being a transcranial nerve regulation technology. There have been attempts by researchers to directly interfere with sympatholytic transmitters using electrical stimulation on a mouse model to interfere with local inflammation using an electrode implantation procedure that is transcranium peripancreatic implantation (see fig. 1). However, in the experiment of the present invention, the electrical stimulation method is very traumatic to the mice, multiple organs are routed, the sympathetic nerves are not exposed and separated, only a stimulator is placed near the nerves, and whether the stimulator stimulates the sympathetic nerves or not, the effect of the model is not specific enough, and the route of the route is long, so the present invention does not adopt the transcranial apical current stimulation method. The invention adopts a peripheral sympathetic nerve stimulation model, and realizes the specific intervention on the sympathetic nerve by wrapping the flexible electrode on the peripheral sympathetic nerve of the target section. The model can successfully verify the relationship between the electric stimulation sympathetic nerves and the quantity of inflammatory factors.
The term "tendon adhesion" used in the present invention is divided into three phases: inflammatory, proliferative, and remodelling phases. Inflammation is an acute response after injury, and the release of various cytokines allows fibroblasts to be recruited to the site of injury, secrete various extracellular matrices, and adhere tendons to surrounding tissues while repairing the tendons. During the remodeling stage, the injured tendon will re-divide the internal collagen proportion so that the injured tendon can recover the pre-injury form, but all the current approaches cannot completely repair the tendon.
Example 1 relation of sympatholytic Electrical stimulation to inflammatory factors
1. The mice were anesthetized, prepared and the skin of the waist section was fully exposed.
2. Anatomical features of mouse lumbar sympathetic nerve: the thoracic sympathetic nerves are symmetrically distributed at the front and outer sides of the thoracic vertebrae to form two bundles after reaching the lumbar vertebrae, and run between the diaphragmatic muscle dead points and the lumbar muscle at the left front side of the lumbar vertebrae.
3. Exposing and isolating sympathetic nerves: in the prone position of the mouse, an incision of about 1.5cm is cut by 5mm on the left side of the middle, the posterior layer of thoracolumbar fascia is longitudinally separated along the lumbar spinous process, the erector spinal muscle is seen, and a weak part at the junction of the erector spinal muscle and the internal oblique muscle is found to make a longitudinal incision, so that the left kidney wrapped by the peritoneum is seen. The right lateral position of the mice was separated from the peritoneum along the left kidney to the inside under a split microscope at 12.5 x magnification with the aid of a retractor until the abdominal aorta was seen. The visual field of the abdominal aorta layer is fully exposed, the sympathetic nerve is positioned at the deep layer of the abdominal aorta by about 5mm, the sympathetic nerve presents segmental expansion, and the abdominal aorta branch runs inwards from the 2 nd section to the 3 rd section of the lumbar section sympathetic nerve and is separated upwards from the 4 th section to the 5 th section of the deep part of the kidney.
4. Embedding the electrode, wrapping the flexible electrode on the sympathetic nerve of the target segment, and realizing the specific intervention on the sympathetic nerve. Setting parameters of electric stimulation as follows: 1mA 10Hz, the duration of the stimulation was 15 minutes.
5. Then, the mouse tenaculum digitorum is sutured after being cut off, and the materials are obtained 1.5 hours after suturing, namely, the tissue around the tendon of the modeling part of the mouse is not included in the tendon itself, and the inflammatory factor change after tendon injury is detected.
6. Electrode implantation, tendon modeling, tissue sampling and experimental group operation were identical in the control group, but no electrical stimulation was given.
Experimental results:
As shown in fig. 2, the method is suitable for the clinical transformation of surgical electrode implantation mode, and has small damage and stronger specificity aiming at the dissection of the mouse sympathetic nerves. The various segments of the sympathetic nerve are exposed under the scope, i.e. the travelling sympathetic nerve is found between the stop points of the psoas and the diaphragm, which makes the intervention means more specific, and the operation mode is similar to the mode of the retroperitoneal access under the laparoscope in clinic, so that the subsequent clinical transformation is facilitated.
After finding the sympathetic nerve running between the lumbar and diaphragmatic dead points, electrodes are implanted and then sutured, as shown in fig. 3.
As shown in fig. 4, the stitching indicates that the working electrode is on the back.
As shown in FIG. 5, the electric stimulation group can effectively reduce inflammation indexes such as TNFa, IL-6 and the like around tendon injury after electric stimulation (wt: control group; ES: electric stimulation group) (graphs A, B). Meanwhile, when the stimulation frequency is kept unchanged at 10Hz, different currents are applied in a gradient mode, the change of TNF-alpha indexes is detected, and the effect of electric stimulation on reducing local inflammation of mice is found to be most obvious in a 0.3-3 mA interval (graph C).
Claims (10)
1. Use of electrical stimulation in the manufacture of an apparatus for treating tissue damage, characterized in that the use comprises reducing inflammation and/or tissue adhesion prevention caused by tissue damage.
2. Use of electrical stimulation according to claim 1, in the manufacture of a device for the treatment of tissue injuries, such as mechanical injuries of soft tissues like ligaments, articular cartilage, skeletal muscle, and inflammatory reactions caused by injuries; the inflammatory reaction of the tissue has a great deal of proliferation of fibroblasts, collagen fibers are generated, the collagen fibers invade the damaged part to finish exogenous repair, adhesion is formed, local adhesion can form pain points, and pain is finally caused.
3. Use of electrical stimulation according to claim 1, characterized in that the inflammatory factors, such as interleukins (interleukin, IL), interferons (IFN) and tumour necrosis factors (tumornecrosisfactor, TNF) are increased at the site of the injury.
4. Use of electrical stimulation according to claim 1 for the manufacture of an apparatus for the treatment of tissue damage, characterized in that the electrical stimulation refers to electrical stimulation of nerve tissue, such as sympathetic nerve tissue, at the damaged tissue, with electrical stimulation parameters: 0.3-3 mA, 10-50 Hz, and the duration of the stimulus is 5-20 minutes.
5. Use of electrical stimulation according to claim 1, in the manufacture of an instrument for the treatment of tissue damage, characterized in that the electrical stimulation comprises transcutaneous electrical stimulation and regulatable implantable electrical stimulation.
6. An electro-stimulation therapy apparatus for acting on nerve tissue, such as sympathetic nerve tissue, at damaged tissue, characterized in that the electro-stimulation therapy apparatus comprises a power source, a memory, electrodes and connecting wires thereof.
7. The electro-stimulation therapy apparatus of claim 6, wherein said electrode is sheet-like or needle-like.
8. The electro-stimulation therapeutic apparatus as defined in claim 6, wherein the sheet electrode is applied to the skin surface of the damaged tissue, and reduces inflammatory factors at the affected part by electro-stimulation of sympathetic nerves at the damaged tissue, thereby reducing damage to the tissue, preventing tendon adhesion, and promoting healing.
9. The electro-stimulation therapy apparatus of claim 6, wherein the sheet electrode is implanted in subcutaneous tissue at the lesion, and reduces inflammatory factors at the lesion by electro-stimulation of sympathetic nerves at the lesion tissue, thereby reducing tissue damage, preventing tendon adhesion, and promoting healing.
10. The electro-stimulation therapy apparatus of claim 6, wherein the electrode is a needle electrode, the needle electrode is fixed on a substrate, a plurality of insertion holes for the needle electrode are arranged on the substrate, and the number of the insertion electrodes on the substrate is determined according to the size of the skin area of the affected part.
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