# A Study on THE Mechanism of Electroacupuncture to Alleviate Visceral Pain and NGF Expression

Authors: Dongdong Liang; Yelong Ren; Ledan Huang; Shenhui Jin
Journal: Computational Intelligence and Neuroscience
 (2022)

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## Abstract

Visceral pain is unbearable, and natural methods are needed to relieve it. Electroacupuncture is a relatively new technique that helps relieve visceral pain by improving blood circulation and providing energy to clogged parts of the body. However, its analgesic effect and mechanism in colorectal pain are still unknown. In this study, the visceral pain models of electroacupuncture in rats were compared and discussed, using nanocomponents to stimulate the expression and mechanism of the nerve growth factor in colorectal pain and electroacupuncture and to observe the expression and mechanism of nerve growth factor in visceral pain relief rats induced by nanocomponents and electroacupuncture. The results show that nanocomponents can effectively relieve visceral pain under the action of electroacupuncture. NGF can activate endogenous proliferation, migration, differentiation, and integration. NSC can promote nerve regeneration and recovery after injury.


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## Body

## 1. Introduction

Electroacupuncture can be used for long-term stimulation of one or more waveforms of the same intensity or varying intensity [1]. Therefore, it also has the function of traditional acupuncture and moxibustion, namely, to dig the channels and collaterals and coordinate, and it also has the electric current stimulation effect [2, 3]. It can act on some painful parts of the body surface and has an immediate analgesic effect, i.e., long time, poor analgesic effect. The spare wave can cause muscle contraction, produce a strong sense of tremor, improve muscle ligament tension, regulate vasomotor function, improve blood circulation, promote recovery of neuromuscular function, and have a good therapeutic effect on neuromuscular paralysis [4, 5]. The density wave is a combination of density wave and density wave. The duration of density is about 1.5 s. It can produce immediate and delayed inhibition in sensory and motor nerves, play a strong role in analgesia and maintenance, and the tissue is not able to easily produce an adaptive response. It is commonly used in acupuncture analgesia. By adjusting the frequency, continuous waves become a single sparse wave or dense wave [6, 7]. In the form of dense wave, the pain was relieved immediately, and in the form of sparse wave, the pain relief effect was maintained again, and the wave width is the same, and the patient is not uncomfortable. The intermittent wave can improve muscle excitability, but it has no obvious analgesic effect. Irritable bowel syndrome (IBS) is a typical representative of chronic functional visceral pain [8].After acupoint electroacupuncture treatment, the synthesis and utilization of norepinephrine is accelerated, but the utilization speed is faster than the synthesis speed [9]. The effects of acupuncture on the content of E and NE in plasma are closely related. The effect of acupuncture on a patient with the decrease of the content of E and NE in plasma is better, and the effect on a patient with more release is worse [10, 11]. Low-frequency 2 Hz electroacupuncture can release a lot of enkephalin in the spinal cord, and high-frequency 100 Hz electroacupuncture can release a lot of enkephalin in the spinal cord [12]. The 2–100 Hz density wave can cause the release of enkephalin and myorphine simultaneously. Enkephalin and muscle enkephalin enhance each other and have a strong analgesic effect on pain caused by visceral stimulation [13].In the central nervous system, there are not only pain centers with nociceptive stimulation but also downward regulating systems, which deal with various stimulation information and are related to analgesia [14]. As we all know, the stimulation of entering the spinal cord pain is transmitted through the peripheral nerve, and then from the brainstem and thalamus, limbic system and cerebral cortex on the new and old spinal cord tract, and other stimulation information integration and processing at all levels of the center, finally produce the emotional response of pain and pain [15]. Acupuncture is believed to not only inhibit the transmission of pain information from the spinal cord to the central system but also inhibit pain and pain response by stimulating the human body’s neurohumoral and pain-regulating system so as to play an analgesic role [16]. However, its analgesic effect and mechanism in colorectal pain are still unknown.In this study, the visceral pain models of electroacupuncture in rats were compared and discussed, using nanocomponents to stimulate the expression and mechanism of nerve growth factor in colorectal pain and electroacupuncture and to observe the expression and mechanism of nerve growth factor in visceral pain relief rats induced by nanocomponents and electroacupuncture. The results show that nanocomponents can effectively relieve visceral pain under the action of electroacupuncture. NGF can activate endogenous proliferation, migration, differentiation, and integration. NSC can promote nerve regeneration and nerve function recovery after injury.


## 2. Literature Review

### 2.1. Visceral Pain in Rats

There are peripheral and central sensitization mechanisms in visceral hypersensitivity, but most previous studies are limited to the peripheral sensitization mechanism and lack of understanding of the role of spinal cord, especially the central level above the spinal cord. Neurotransmitters 5-hydroxytryptamine (5-HT), calcitonin gene-related peptide (CGRP), and nitric oxide in the visceral sensory pathway play an important role in the spinal cord and above [17, 18]. It can be seen that the formation of visceral sensation is a complex process, and the viscera, spinal cord, and above ones participate in the perception of visceral stimulation. Acupuncture is an effective way to treat pain. However, as the response point and stimulation point of acupuncture diagnosis and treatment, the essence and mechanism of acupuncture point are not clear.“Zusanli” and “Shangjuxu” are commonly used acupoints in clinical treatment of gastrointestinal diseases [19]. Acupuncture can stimulate a variety of receptors, produce acupuncture signals, and reach the spinal cord, medulla oblongata, thalamus, and cerebral cortex through different ways [20]. The spinal cord is the first station to deal with and translate acupuncture analgesia; the brainstem is the relay station of forepart, syndrome differentiation, stimulation, synthesis, and transfixion, which plays an important role in acupuncture analgesia; the thalamus part is the coordination center to strengthen acupuncture analgesia and control analgesia, with a variety of neurohumoral system involved in complex analysis and comprehensive regulation of various information; the limbic system, its nucleus, and various neurotransmitters play a coordinating role in acupuncture analgesia; and the cerebral cortex is the highest center, which is not only a process of excitation and inhibition but also a complex center of regulation and command, which can not only strengthen analgesia but also inhibits excessively and play a role in maintaining dynamic balance [21, 22]. Electroacupuncture is based on the development of acupuncture and the theory of modern electronic medicine.The CGRP expression in the trigeminal sensory nucleus, the raphe nucleus, and the solitary tract nucleus of visceral hypersensitive rats increased [23]. CGRP is widely distributed in the sensory nerve fiber endings and tissues of the central and peripheral nervous systems of mammals and humans. The content of CGRP in the central nervous system is the highest in the thalamus and other regions. The functions of different brain regions of CGRP can be completely reversed; the part of the nucleus of neurons expressing CGRP is the place where the visceral primary afferent nerve stops directly, which is related to pain conduction, while a part of the nucleus which inhibits the transmission of the pain nerve and plays an analgesic role, and there is a fiber connection between these nuclei [24, 25].According to the latest research data, neurotrophic factors have many functions. In the process of nerve regeneration, it can guide the growth of axon, stimulate the growth of axon, and reduce the risk of neuron damage. The external intervention of the above neurotrophic factors shows that neurotrophic factors can promote neuronal regeneration, protect the damage of neurons, and play a certain role in axon regeneration and guidance of axons. In the past, it was thought that the central nervous system could not regenerate after axon injury due to the lack of neurotrophic factors in the microenvironment. Under the promotion of 5-transtryptamine (5-HT), neurons precursor cells began to differentiate into neurons. Moreover, it can promote the differentiation of cortical neurons and hippocampal neurons. Only after cerebral ischemia, the release of 5-HT will increase to meet the needs of the body and participate in the regulation of neurons. It can be seen that there are many injury factors and anti-injury factors in the ischemic brain tissue after cerebral infarction. They coexist and influence each other. Among these factors, some can be intervened by people, some cannot be intervened by people, at least there is no way to intervene at present. There are many factors that can be intervened in, such as the neurotrophic factor, nerve regeneration inhibitory factor, nerve regeneration guiding factor, and so on.


### 2.2. Electroacupuncture

Electroacupuncture has a good regulatory effect on neurotrophic factors after cerebral ischemia, so we consider whether we can use electroacupuncture to promote the proliferation of NSC in the brain to carry out the treatment of endogenous activation treatment. After cerebral ischemia, electroacupuncture can effectively stimulate hippocampal neurons, activate the proliferation of hippocampal neurons, and finally restore the neural function of the brain.At the beginning, traditional Chinese medicine put forward the mechanism of electroacupuncture and described it very clearly. Western medicine is not mature, and the understanding is not in-depth but more just for the metabolism of the body. For example, electroacupuncture can regulate abnormalities of hemorheology, blood lipids, and neurobiochemistry, indirectly improve brain oxygen and energy metabolism or directly expand blood vessels, promote the formation of new blood vessels, and increase local brain oxygen. However, there are few studies on its deep cellular and molecular mechanism.Electroacupuncture can produce nerve conduction impulses and transmit them in the form of electric energy, which can adjust the excitability of the reached parts and affect the electrical activity of the brain. Like any other tissue and cell regeneration, nerve regeneration includes three stages such as proliferation, migration, and differentiation, which belong to the basic development process of the body. In the stage of cell proliferation, the NSC divides asymmetrically with the proliferation of neural precursor cells. Then neural precursor cells begin to proliferate, migrate, and differentiate. The final result of differentiation is the production of mature neural cells. Adult central nerve regeneration plays a role in the treatment of brain injury and participates in some pathological processes. After brain injury, some factors can stimulate the proliferation and differentiation of neural precursor cells and then migrate to the injured site to play a role instead of the injured cells. Whether it is systemic or focal cerebral ischemia, the central nervous system of the adult brain has this function, which is regulated by the body. In order to stimulate the proliferation and differentiation of precursor cells and form new nerve cells, growth factors were injected. The newly formed neurons have the neuron function. They can also differentiate to meet the needs of the body, receive and send pulses, and then improve the neurological function. When the brain is injured, after a series of complex reactions, it can rapidly stimulate the proliferation and differentiation of neural precursor cells. Therefore, regeneration of the brain nerve that receives signals is the expression ability of the brain, plays a role in its own repair, and plays a role in the treatment process.After cerebral ischemia, the expression of the NTF gene was activated. In the early stage of ischemia, the NTF gene expression is the most obvious, usually within minutes to hours, but the expression will not last for a long time and will soon return to the original state.At present, acupuncture analgesia has been used in the treatment of acute and chronic abdominal pain, headache, dysmenorrhea, chronic inflammatory arthralgia, and other sporadic reports, as well as in appendectomy, thyroidectomy, assisted major surgery analgesia, and other related reports. The operation of acupuncture analgesia has some disadvantages, such as lack of pain control, muscle tension, and visceral traction reaction, but the requirement of an auxiliary examination, such as enteroscopy, is relatively low. Acupuncture stimulates the transmission of direct type I and type II afferent nerve fibers to pass through these fibers, and muscles and nerve impulses are transmitted to the anterior and lateral sides of the spinal cord, thereby preventing pain signals from being transmitted up to the spinal tract. Acupuncture stimulates the midbrain-related nuclei by activating the gray matter cells around the aqueduct and the spinal cord nucleus and then transmits signals downward through the dorsolateral tract to reduce the release of norepinephrine and serotonin in the spinal cord. These neurotransmitters inhibit presynaptic and postsynaptic space pain stimulation by inhibiting signal transduction of the spinal thalamic tract. In the pituitary hypothalamic system, acupuncture signals promote enkephalin and adrenocorticotropic hormones to enter the blood.Acupuncture can also activate the GABA receptor, release the substance P, activate the secretion of vasopressin in the paraventricular nucleus of the hypothalamus, and participate in pain inhibition. The nerve endings and the peripheral autonomic nervous system form a synaptic network in the gastric wall. When the digestive tract is stimulated by the injury, the body can feel and transmit the pain through the activities of internal ENS and pan, and change the intestinal motility and functional structure of the ENS through the intestinal reflex pathway. NOS plays an important role in the transmission and regulation of harmful information in the nervous system. In intestinal motility, NOS is a strong inhibitory transmitter. When the intestinal tract is stimulated by injury, no catalysis-produced blood vessels can relax. NOS can protect the intestinal mucosa by increasing the blood flow of the gastric mucosa.


### 2.3. NGF Expression Mechanism

Because the adult central nervous system can regenerate and respond to various brain injuries, it has great clinical application value and provides a new treatment basis for the treatment and rehabilitation of brain injury diseases. Its mechanism is to promote the regeneration of adult central nervous system by activating neural precursor cells. Clinically, it is considered that the embryonic central nervous system is the most regenerated, and the mature central nervous system is composed of differentiated and mature nerve cells. Due to external or internal reasons, it is not easy to regenerate after stimulation and repair after injury. Neurotrophic factors play an important role in nerve regeneration.NGF is the most important bioactive substance in the central nervous system. Increased expression of endogenous NGF in the ischemic brain has a protective effect on neurons. It can resist hypoxia, hypoglycemia, and nitric oxide damage, and effectively protect neurons. Therefore, intraperitoneal injection of exogenous NGF can effectively protect rats and reduce the probability of hypoxic-ischemic brain damage. Neurotrophic factor is a kind of soluble peptide factor that can provide nutrition. It can create a suitable microenvironment for the nervous system and play a role. The condition of producing the neurotrophic function is to combine with the corresponding receptor. In the mother, the normal development of the nervous system and the survival of neurons cannot be completed by themselves, which requires a kind of NTF to maintain and can induce the growth direction of the nerve process. After birth, NTF plays an important role in maintaining and regulating various functions and normal physiology of the nervous system.Neurotrophic factors are not the determinants of axon growth because even if there are neurotrophic factors in the experiment, axons of neurons are still difficult to regenerate, and the peripheral nerve and central nerve can regenerate under the same conditions. These inhibitory proteins exist mainly in the white matter of the central nervous system, inhibit the growth of nerve processes, prevent the growth of ganglion cells, cause atrophy of nerve fibers, and make nerve fibers unable to grow. NSCs, as the basis for the development of mature central nervous system, have the ability for proliferation, differentiation, self-replication, and rapid increase of the number of daughter cells. Like stem cells, the subcellular groups formed by self-replication can self-differentiate and get mature to a certain extent, and the result of differentiation is the formation of various types of cells in the neural tissue. When the brain is damaged, these neural precursor cells can differentiate into neurons and glial cells and play a role. This differentiationability is permanent. NSCs can be reproduced and proliferated under suitable environmental conditions. NSCs can further differentiate and form mature new neurons after replicating to a certain number. However, the adult newborn neurons are unstable and susceptible to various factors. The neurotransmitter, through the conversion of energy, is the medium of transmitting the signal and pulse signal. Furthermore, it can effectively promote NSC proliferation and differentiation of NSC, but the effect of neurotransmitters on NSC changes with the situation, which is different from the normal state of cerebral ischemia.


## 2.1. Visceral Pain in Rats

There are peripheral and central sensitization mechanisms in visceral hypersensitivity, but most previous studies are limited to the peripheral sensitization mechanism and lack of understanding of the role of spinal cord, especially the central level above the spinal cord. Neurotransmitters 5-hydroxytryptamine (5-HT), calcitonin gene-related peptide (CGRP), and nitric oxide in the visceral sensory pathway play an important role in the spinal cord and above [17, 18]. It can be seen that the formation of visceral sensation is a complex process, and the viscera, spinal cord, and above ones participate in the perception of visceral stimulation. Acupuncture is an effective way to treat pain. However, as the response point and stimulation point of acupuncture diagnosis and treatment, the essence and mechanism of acupuncture point are not clear.“Zusanli” and “Shangjuxu” are commonly used acupoints in clinical treatment of gastrointestinal diseases [19]. Acupuncture can stimulate a variety of receptors, produce acupuncture signals, and reach the spinal cord, medulla oblongata, thalamus, and cerebral cortex through different ways [20]. The spinal cord is the first station to deal with and translate acupuncture analgesia; the brainstem is the relay station of forepart, syndrome differentiation, stimulation, synthesis, and transfixion, which plays an important role in acupuncture analgesia; the thalamus part is the coordination center to strengthen acupuncture analgesia and control analgesia, with a variety of neurohumoral system involved in complex analysis and comprehensive regulation of various information; the limbic system, its nucleus, and various neurotransmitters play a coordinating role in acupuncture analgesia; and the cerebral cortex is the highest center, which is not only a process of excitation and inhibition but also a complex center of regulation and command, which can not only strengthen analgesia but also inhibits excessively and play a role in maintaining dynamic balance [21, 22]. Electroacupuncture is based on the development of acupuncture and the theory of modern electronic medicine.The CGRP expression in the trigeminal sensory nucleus, the raphe nucleus, and the solitary tract nucleus of visceral hypersensitive rats increased [23]. CGRP is widely distributed in the sensory nerve fiber endings and tissues of the central and peripheral nervous systems of mammals and humans. The content of CGRP in the central nervous system is the highest in the thalamus and other regions. The functions of different brain regions of CGRP can be completely reversed; the part of the nucleus of neurons expressing CGRP is the place where the visceral primary afferent nerve stops directly, which is related to pain conduction, while a part of the nucleus which inhibits the transmission of the pain nerve and plays an analgesic role, and there is a fiber connection between these nuclei [24, 25].According to the latest research data, neurotrophic factors have many functions. In the process of nerve regeneration, it can guide the growth of axon, stimulate the growth of axon, and reduce the risk of neuron damage. The external intervention of the above neurotrophic factors shows that neurotrophic factors can promote neuronal regeneration, protect the damage of neurons, and play a certain role in axon regeneration and guidance of axons. In the past, it was thought that the central nervous system could not regenerate after axon injury due to the lack of neurotrophic factors in the microenvironment. Under the promotion of 5-transtryptamine (5-HT), neurons precursor cells began to differentiate into neurons. Moreover, it can promote the differentiation of cortical neurons and hippocampal neurons. Only after cerebral ischemia, the release of 5-HT will increase to meet the needs of the body and participate in the regulation of neurons. It can be seen that there are many injury factors and anti-injury factors in the ischemic brain tissue after cerebral infarction. They coexist and influence each other. Among these factors, some can be intervened by people, some cannot be intervened by people, at least there is no way to intervene at present. There are many factors that can be intervened in, such as the neurotrophic factor, nerve regeneration inhibitory factor, nerve regeneration guiding factor, and so on.


## 2.2. Electroacupuncture

Electroacupuncture has a good regulatory effect on neurotrophic factors after cerebral ischemia, so we consider whether we can use electroacupuncture to promote the proliferation of NSC in the brain to carry out the treatment of endogenous activation treatment. After cerebral ischemia, electroacupuncture can effectively stimulate hippocampal neurons, activate the proliferation of hippocampal neurons, and finally restore the neural function of the brain.At the beginning, traditional Chinese medicine put forward the mechanism of electroacupuncture and described it very clearly. Western medicine is not mature, and the understanding is not in-depth but more just for the metabolism of the body. For example, electroacupuncture can regulate abnormalities of hemorheology, blood lipids, and neurobiochemistry, indirectly improve brain oxygen and energy metabolism or directly expand blood vessels, promote the formation of new blood vessels, and increase local brain oxygen. However, there are few studies on its deep cellular and molecular mechanism.Electroacupuncture can produce nerve conduction impulses and transmit them in the form of electric energy, which can adjust the excitability of the reached parts and affect the electrical activity of the brain. Like any other tissue and cell regeneration, nerve regeneration includes three stages such as proliferation, migration, and differentiation, which belong to the basic development process of the body. In the stage of cell proliferation, the NSC divides asymmetrically with the proliferation of neural precursor cells. Then neural precursor cells begin to proliferate, migrate, and differentiate. The final result of differentiation is the production of mature neural cells. Adult central nerve regeneration plays a role in the treatment of brain injury and participates in some pathological processes. After brain injury, some factors can stimulate the proliferation and differentiation of neural precursor cells and then migrate to the injured site to play a role instead of the injured cells. Whether it is systemic or focal cerebral ischemia, the central nervous system of the adult brain has this function, which is regulated by the body. In order to stimulate the proliferation and differentiation of precursor cells and form new nerve cells, growth factors were injected. The newly formed neurons have the neuron function. They can also differentiate to meet the needs of the body, receive and send pulses, and then improve the neurological function. When the brain is injured, after a series of complex reactions, it can rapidly stimulate the proliferation and differentiation of neural precursor cells. Therefore, regeneration of the brain nerve that receives signals is the expression ability of the brain, plays a role in its own repair, and plays a role in the treatment process.After cerebral ischemia, the expression of the NTF gene was activated. In the early stage of ischemia, the NTF gene expression is the most obvious, usually within minutes to hours, but the expression will not last for a long time and will soon return to the original state.At present, acupuncture analgesia has been used in the treatment of acute and chronic abdominal pain, headache, dysmenorrhea, chronic inflammatory arthralgia, and other sporadic reports, as well as in appendectomy, thyroidectomy, assisted major surgery analgesia, and other related reports. The operation of acupuncture analgesia has some disadvantages, such as lack of pain control, muscle tension, and visceral traction reaction, but the requirement of an auxiliary examination, such as enteroscopy, is relatively low. Acupuncture stimulates the transmission of direct type I and type II afferent nerve fibers to pass through these fibers, and muscles and nerve impulses are transmitted to the anterior and lateral sides of the spinal cord, thereby preventing pain signals from being transmitted up to the spinal tract. Acupuncture stimulates the midbrain-related nuclei by activating the gray matter cells around the aqueduct and the spinal cord nucleus and then transmits signals downward through the dorsolateral tract to reduce the release of norepinephrine and serotonin in the spinal cord. These neurotransmitters inhibit presynaptic and postsynaptic space pain stimulation by inhibiting signal transduction of the spinal thalamic tract. In the pituitary hypothalamic system, acupuncture signals promote enkephalin and adrenocorticotropic hormones to enter the blood.Acupuncture can also activate the GABA receptor, release the substance P, activate the secretion of vasopressin in the paraventricular nucleus of the hypothalamus, and participate in pain inhibition. The nerve endings and the peripheral autonomic nervous system form a synaptic network in the gastric wall. When the digestive tract is stimulated by the injury, the body can feel and transmit the pain through the activities of internal ENS and pan, and change the intestinal motility and functional structure of the ENS through the intestinal reflex pathway. NOS plays an important role in the transmission and regulation of harmful information in the nervous system. In intestinal motility, NOS is a strong inhibitory transmitter. When the intestinal tract is stimulated by injury, no catalysis-produced blood vessels can relax. NOS can protect the intestinal mucosa by increasing the blood flow of the gastric mucosa.


## 2.3. NGF Expression Mechanism

Because the adult central nervous system can regenerate and respond to various brain injuries, it has great clinical application value and provides a new treatment basis for the treatment and rehabilitation of brain injury diseases. Its mechanism is to promote the regeneration of adult central nervous system by activating neural precursor cells. Clinically, it is considered that the embryonic central nervous system is the most regenerated, and the mature central nervous system is composed of differentiated and mature nerve cells. Due to external or internal reasons, it is not easy to regenerate after stimulation and repair after injury. Neurotrophic factors play an important role in nerve regeneration.NGF is the most important bioactive substance in the central nervous system. Increased expression of endogenous NGF in the ischemic brain has a protective effect on neurons. It can resist hypoxia, hypoglycemia, and nitric oxide damage, and effectively protect neurons. Therefore, intraperitoneal injection of exogenous NGF can effectively protect rats and reduce the probability of hypoxic-ischemic brain damage. Neurotrophic factor is a kind of soluble peptide factor that can provide nutrition. It can create a suitable microenvironment for the nervous system and play a role. The condition of producing the neurotrophic function is to combine with the corresponding receptor. In the mother, the normal development of the nervous system and the survival of neurons cannot be completed by themselves, which requires a kind of NTF to maintain and can induce the growth direction of the nerve process. After birth, NTF plays an important role in maintaining and regulating various functions and normal physiology of the nervous system.Neurotrophic factors are not the determinants of axon growth because even if there are neurotrophic factors in the experiment, axons of neurons are still difficult to regenerate, and the peripheral nerve and central nerve can regenerate under the same conditions. These inhibitory proteins exist mainly in the white matter of the central nervous system, inhibit the growth of nerve processes, prevent the growth of ganglion cells, cause atrophy of nerve fibers, and make nerve fibers unable to grow. NSCs, as the basis for the development of mature central nervous system, have the ability for proliferation, differentiation, self-replication, and rapid increase of the number of daughter cells. Like stem cells, the subcellular groups formed by self-replication can self-differentiate and get mature to a certain extent, and the result of differentiation is the formation of various types of cells in the neural tissue. When the brain is damaged, these neural precursor cells can differentiate into neurons and glial cells and play a role. This differentiationability is permanent. NSCs can be reproduced and proliferated under suitable environmental conditions. NSCs can further differentiate and form mature new neurons after replicating to a certain number. However, the adult newborn neurons are unstable and susceptible to various factors. The neurotransmitter, through the conversion of energy, is the medium of transmitting the signal and pulse signal. Furthermore, it can effectively promote NSC proliferation and differentiation of NSC, but the effect of neurotransmitters on NSC changes with the situation, which is different from the normal state of cerebral ischemia.


## 3. Experiment Set-Up

### 3.1. Research Object

Six nests of clean newborn SD rats were divided into three groups. From the 8th day of birth, the model rats were given 60 mmHg of colorectal distention stimulation every afternoon, once a day for seven consecutive days; the lactating rats were raised in the same cage with the mother rats and separated from the mother rats after 21 days; the normal control group was not given colorectal distention stimulation, and other treatments were the same as the model group. The rats were fed with mixed formula for 8 weeks. They can eat and drink freely and change drinking water and feed every day to keep the living environment ventilated and clean. Observe your diet, drinking water, activities, and defecation to ensure their health and avoid all kinds of harmful stimulation. They were randomly divided into model group, control group, and electroacupuncture group. Rats in the normal control group were treated the same as those in the model group.


#### 3.1.1. Main Instrument Parameters

The list of main instruments is shown in Table1.Table 1
List of main instruments.
Equipment nameInstrument manufacturerRat tail cuff blood pressure meter (BP-98A)Japan Softron corporationElectric heating constant temperature drying oven (202-1)Shanghai Lunan scientific instrument factoryImage-Pro Plus 6.0 Image Analysis SystemMedia cyberneticsElectrotherapyKang Ling company


### 3.2. Experimental Plan

The establishment of chronic visceral pain model was done by stimulating Sprague-Dawley rats by colorectal distention once a day when awake, 6–10 days after birth. The CRD method is done by maintaining the pressure for 1 min, deflate, and then retract the balloon. Before expansion stimulation, 0.5 ml physiological water can be used for enema and defecation in advance to reduce the influence of fecal quality on expansion degree. After the modeling, the normal feeding was done for 8 weeks, and the experiment started.


#### 3.2.1. Behavioral Evaluation

At the age of 8 weeks, the sensitivity of visceral pain in rats was evaluated by the scores of absolute with rawalreflex (AWR) stimulated by CRD. The picture of a rat posing during the CRD experiment is shown in Figure1.Figure 1
CRD experiment in rats.Before the experiment, the rats fasted for 18 hours. After anesthesia with ether, the self-made wax-coated air bag was inserted into the colorectal part, and the end of the air bag was 1.0 cm deep from the anus, and the catheter was fixed at the place 1.0 cm away from the anus by the adhesive tape. The catheter is connected to a syringe and a sphygmomanometer through a three-way pipe. The rats were placed in a plexiglass observation box. Before and after the experiment, the mice could move freely but could not turn around. The experiment began 30 minutes after the rats woke up and were fully adapted to the environment. Air was injected from low pressure gradient to high pressure gradient, and the pressure in the balloon reached 20 mmHg, 40 mmHg, 60 mmHg, and 80 mmHg, respectively. The expansion time is 20 s, the interval is 4 minutes, and the pressure is repeated three times. The average of the three scores is taken as the result. The single-blind method was used to evaluate the AWR intensity under various pressures. Scoring standard can be given as follows: 0, no obvious behavior change during colon expansion; 1, the body is still or simple head movement during colon expansion; 2, the abdominal muscle began to contract during colon expansion, but the abdominal muscle did not leave the platform; 3, the abdominal muscle obviously contracted to become flat during colon expansion or the lower abdominal wall from the bottom of the box; 4,+ when colon expansion, the abdominal wall arched or is accompanied by body uplift, pelvis bent, or testicles raised.


#### 3.2.2. Measurement of Extraabdominal Obliquity

When the rats are 6 weeks old, CRD stimulation was used to measure extraabdominal obliquity and evaluate visceral pain sensitivity. After the balloon was implanted as described above, the rats were fixed on the operating table, and the electrode needle was inserted into the lateral oblique muscle 1.5 cm above the inguinal ligament. The experiment began 30 minutes after the rats woke up and were fully adapted to the environment. Air was injected from low to high gradient, and the pressure in the balloon reached 20 mmHg, 40 mmHg, 60 mmHg, and 80 mmHg, respectively. Each expansion lasts for 10 s, and the interval between the two pressures is 4 min. The RM6240BD multichannel physiological signal acquisition and processing system was used to record the discharge activity of rat abdominal external oblique muscle under different CRD pressure (parameter setting: high-frequency filtering 3 kHz, time constant 0.001 s, sampling frequency 40 Hz, sensitivity 500 uv, paper speed 200 ms/div). The experimental environment is quiet, and the relative humidity is within 40–70%, and the room temperature is within 23–27°C.


#### 3.2.3. Electroacupuncture

The acupuncture method was done according to the standard acupuncture method, and the rats were fixed. According to the needs of the experiment, choose Baihui and Dazhui points for electroacupuncture treatment with an electroacupuncture treatment instrument. Baihui is located at the intersection of the middle line of the head and the line connecting the two ear tips, and Dazhui is located under the spinous process of the seventh cervical vertebra. The spinous process of the seven cervical vertebrae is located behind the bowed head under the largest package of the neck. The picture of the electroacupuncture instrument is shown in Figure2.Figure 2
Picture of electroacupuncture.


#### 3.2.4. Acupuncture Method

Use the 31l inch filiform needle, and after finding the right position, prick the acupoints along the direction of the skin, and the depth of acupuncture is moderate, about 2.5–3.5 mm. The needle handle is connected with the electrode of the electroacupuncture instrument. The strength of the electroacupuncture instrument is adjusted to 3.5 V, and the frequency is 4 Hz. Then close observation is required. The appropriate standard is a slight twitch of the animal’s muscles, without struggling and neighing for 10 minutes. The electroacupuncture group can be treated once a day for 14 consecutive days on the day the animal model and after the animal awakes. The density wave was used in the electroacupuncture treatment instrument. CRD was stimulated immediately after electroacupuncture, and the changes of AWR and EMG were observed, and the therapeutic effect of electroacupuncture was evaluated.


#### 3.2.5. Computer Image Analysis

The BX51 digital microscope camera system collects the images of each spinal cord section and magnifies them by 20 times. Under the same multiple, each section randomly selected three fields of vision, and the computer image analysis system was applied to semiquantitative analysis of the grayscale integral value of immune positive cells. The smaller the grayscale integral value, the stronger the tissue staining.


#### 3.2.6. Statistical Analysis

The data were calculated by mean ± standard deviation. The standard of significance test isa = 0.05. SPSS11.5 was used for statistical analysis. In order to eliminate the influence of different basic discharges on the experimental results, the basic discharge amplitudes of young rats under the pressure of 20 mmHg, 40 mmHg, 60 mmHg, and 80 mmHgcrd were subtracted from the basic discharge amplitudes of young rats, and the difference represented the discharge amplitudes of different CRDs. Repeated ANOVA was used to analyze the AWR score and discharge data.


## 3.1. Research Object

Six nests of clean newborn SD rats were divided into three groups. From the 8th day of birth, the model rats were given 60 mmHg of colorectal distention stimulation every afternoon, once a day for seven consecutive days; the lactating rats were raised in the same cage with the mother rats and separated from the mother rats after 21 days; the normal control group was not given colorectal distention stimulation, and other treatments were the same as the model group. The rats were fed with mixed formula for 8 weeks. They can eat and drink freely and change drinking water and feed every day to keep the living environment ventilated and clean. Observe your diet, drinking water, activities, and defecation to ensure their health and avoid all kinds of harmful stimulation. They were randomly divided into model group, control group, and electroacupuncture group. Rats in the normal control group were treated the same as those in the model group.


### 3.1.1. Main Instrument Parameters

The list of main instruments is shown in Table1.Table 1
List of main instruments.
Equipment nameInstrument manufacturerRat tail cuff blood pressure meter (BP-98A)Japan Softron corporationElectric heating constant temperature drying oven (202-1)Shanghai Lunan scientific instrument factoryImage-Pro Plus 6.0 Image Analysis SystemMedia cyberneticsElectrotherapyKang Ling company


## 3.1.1. Main Instrument Parameters

The list of main instruments is shown in Table1.Table 1
List of main instruments.
Equipment nameInstrument manufacturerRat tail cuff blood pressure meter (BP-98A)Japan Softron corporationElectric heating constant temperature drying oven (202-1)Shanghai Lunan scientific instrument factoryImage-Pro Plus 6.0 Image Analysis SystemMedia cyberneticsElectrotherapyKang Ling company


## 3.2. Experimental Plan

The establishment of chronic visceral pain model was done by stimulating Sprague-Dawley rats by colorectal distention once a day when awake, 6–10 days after birth. The CRD method is done by maintaining the pressure for 1 min, deflate, and then retract the balloon. Before expansion stimulation, 0.5 ml physiological water can be used for enema and defecation in advance to reduce the influence of fecal quality on expansion degree. After the modeling, the normal feeding was done for 8 weeks, and the experiment started.


### 3.2.1. Behavioral Evaluation

At the age of 8 weeks, the sensitivity of visceral pain in rats was evaluated by the scores of absolute with rawalreflex (AWR) stimulated by CRD. The picture of a rat posing during the CRD experiment is shown in Figure1.Figure 1
CRD experiment in rats.Before the experiment, the rats fasted for 18 hours. After anesthesia with ether, the self-made wax-coated air bag was inserted into the colorectal part, and the end of the air bag was 1.0 cm deep from the anus, and the catheter was fixed at the place 1.0 cm away from the anus by the adhesive tape. The catheter is connected to a syringe and a sphygmomanometer through a three-way pipe. The rats were placed in a plexiglass observation box. Before and after the experiment, the mice could move freely but could not turn around. The experiment began 30 minutes after the rats woke up and were fully adapted to the environment. Air was injected from low pressure gradient to high pressure gradient, and the pressure in the balloon reached 20 mmHg, 40 mmHg, 60 mmHg, and 80 mmHg, respectively. The expansion time is 20 s, the interval is 4 minutes, and the pressure is repeated three times. The average of the three scores is taken as the result. The single-blind method was used to evaluate the AWR intensity under various pressures. Scoring standard can be given as follows: 0, no obvious behavior change during colon expansion; 1, the body is still or simple head movement during colon expansion; 2, the abdominal muscle began to contract during colon expansion, but the abdominal muscle did not leave the platform; 3, the abdominal muscle obviously contracted to become flat during colon expansion or the lower abdominal wall from the bottom of the box; 4,+ when colon expansion, the abdominal wall arched or is accompanied by body uplift, pelvis bent, or testicles raised.


### 3.2.2. Measurement of Extraabdominal Obliquity

When the rats are 6 weeks old, CRD stimulation was used to measure extraabdominal obliquity and evaluate visceral pain sensitivity. After the balloon was implanted as described above, the rats were fixed on the operating table, and the electrode needle was inserted into the lateral oblique muscle 1.5 cm above the inguinal ligament. The experiment began 30 minutes after the rats woke up and were fully adapted to the environment. Air was injected from low to high gradient, and the pressure in the balloon reached 20 mmHg, 40 mmHg, 60 mmHg, and 80 mmHg, respectively. Each expansion lasts for 10 s, and the interval between the two pressures is 4 min. The RM6240BD multichannel physiological signal acquisition and processing system was used to record the discharge activity of rat abdominal external oblique muscle under different CRD pressure (parameter setting: high-frequency filtering 3 kHz, time constant 0.001 s, sampling frequency 40 Hz, sensitivity 500 uv, paper speed 200 ms/div). The experimental environment is quiet, and the relative humidity is within 40–70%, and the room temperature is within 23–27°C.


### 3.2.3. Electroacupuncture

The acupuncture method was done according to the standard acupuncture method, and the rats were fixed. According to the needs of the experiment, choose Baihui and Dazhui points for electroacupuncture treatment with an electroacupuncture treatment instrument. Baihui is located at the intersection of the middle line of the head and the line connecting the two ear tips, and Dazhui is located under the spinous process of the seventh cervical vertebra. The spinous process of the seven cervical vertebrae is located behind the bowed head under the largest package of the neck. The picture of the electroacupuncture instrument is shown in Figure2.Figure 2
Picture of electroacupuncture.


### 3.2.4. Acupuncture Method

Use the 31l inch filiform needle, and after finding the right position, prick the acupoints along the direction of the skin, and the depth of acupuncture is moderate, about 2.5–3.5 mm. The needle handle is connected with the electrode of the electroacupuncture instrument. The strength of the electroacupuncture instrument is adjusted to 3.5 V, and the frequency is 4 Hz. Then close observation is required. The appropriate standard is a slight twitch of the animal’s muscles, without struggling and neighing for 10 minutes. The electroacupuncture group can be treated once a day for 14 consecutive days on the day the animal model and after the animal awakes. The density wave was used in the electroacupuncture treatment instrument. CRD was stimulated immediately after electroacupuncture, and the changes of AWR and EMG were observed, and the therapeutic effect of electroacupuncture was evaluated.


### 3.2.5. Computer Image Analysis

The BX51 digital microscope camera system collects the images of each spinal cord section and magnifies them by 20 times. Under the same multiple, each section randomly selected three fields of vision, and the computer image analysis system was applied to semiquantitative analysis of the grayscale integral value of immune positive cells. The smaller the grayscale integral value, the stronger the tissue staining.


### 3.2.6. Statistical Analysis

The data were calculated by mean ± standard deviation. The standard of significance test isa = 0.05. SPSS11.5 was used for statistical analysis. In order to eliminate the influence of different basic discharges on the experimental results, the basic discharge amplitudes of young rats under the pressure of 20 mmHg, 40 mmHg, 60 mmHg, and 80 mmHgcrd were subtracted from the basic discharge amplitudes of young rats, and the difference represented the discharge amplitudes of different CRDs. Repeated ANOVA was used to analyze the AWR score and discharge data.


## 3.2.1. Behavioral Evaluation

At the age of 8 weeks, the sensitivity of visceral pain in rats was evaluated by the scores of absolute with rawalreflex (AWR) stimulated by CRD. The picture of a rat posing during the CRD experiment is shown in Figure1.Figure 1
CRD experiment in rats.Before the experiment, the rats fasted for 18 hours. After anesthesia with ether, the self-made wax-coated air bag was inserted into the colorectal part, and the end of the air bag was 1.0 cm deep from the anus, and the catheter was fixed at the place 1.0 cm away from the anus by the adhesive tape. The catheter is connected to a syringe and a sphygmomanometer through a three-way pipe. The rats were placed in a plexiglass observation box. Before and after the experiment, the mice could move freely but could not turn around. The experiment began 30 minutes after the rats woke up and were fully adapted to the environment. Air was injected from low pressure gradient to high pressure gradient, and the pressure in the balloon reached 20 mmHg, 40 mmHg, 60 mmHg, and 80 mmHg, respectively. The expansion time is 20 s, the interval is 4 minutes, and the pressure is repeated three times. The average of the three scores is taken as the result. The single-blind method was used to evaluate the AWR intensity under various pressures. Scoring standard can be given as follows: 0, no obvious behavior change during colon expansion; 1, the body is still or simple head movement during colon expansion; 2, the abdominal muscle began to contract during colon expansion, but the abdominal muscle did not leave the platform; 3, the abdominal muscle obviously contracted to become flat during colon expansion or the lower abdominal wall from the bottom of the box; 4,+ when colon expansion, the abdominal wall arched or is accompanied by body uplift, pelvis bent, or testicles raised.


## 3.2.2. Measurement of Extraabdominal Obliquity

When the rats are 6 weeks old, CRD stimulation was used to measure extraabdominal obliquity and evaluate visceral pain sensitivity. After the balloon was implanted as described above, the rats were fixed on the operating table, and the electrode needle was inserted into the lateral oblique muscle 1.5 cm above the inguinal ligament. The experiment began 30 minutes after the rats woke up and were fully adapted to the environment. Air was injected from low to high gradient, and the pressure in the balloon reached 20 mmHg, 40 mmHg, 60 mmHg, and 80 mmHg, respectively. Each expansion lasts for 10 s, and the interval between the two pressures is 4 min. The RM6240BD multichannel physiological signal acquisition and processing system was used to record the discharge activity of rat abdominal external oblique muscle under different CRD pressure (parameter setting: high-frequency filtering 3 kHz, time constant 0.001 s, sampling frequency 40 Hz, sensitivity 500 uv, paper speed 200 ms/div). The experimental environment is quiet, and the relative humidity is within 40–70%, and the room temperature is within 23–27°C.


## 3.2.3. Electroacupuncture

The acupuncture method was done according to the standard acupuncture method, and the rats were fixed. According to the needs of the experiment, choose Baihui and Dazhui points for electroacupuncture treatment with an electroacupuncture treatment instrument. Baihui is located at the intersection of the middle line of the head and the line connecting the two ear tips, and Dazhui is located under the spinous process of the seventh cervical vertebra. The spinous process of the seven cervical vertebrae is located behind the bowed head under the largest package of the neck. The picture of the electroacupuncture instrument is shown in Figure2.Figure 2
Picture of electroacupuncture.


## 3.2.4. Acupuncture Method

Use the 31l inch filiform needle, and after finding the right position, prick the acupoints along the direction of the skin, and the depth of acupuncture is moderate, about 2.5–3.5 mm. The needle handle is connected with the electrode of the electroacupuncture instrument. The strength of the electroacupuncture instrument is adjusted to 3.5 V, and the frequency is 4 Hz. Then close observation is required. The appropriate standard is a slight twitch of the animal’s muscles, without struggling and neighing for 10 minutes. The electroacupuncture group can be treated once a day for 14 consecutive days on the day the animal model and after the animal awakes. The density wave was used in the electroacupuncture treatment instrument. CRD was stimulated immediately after electroacupuncture, and the changes of AWR and EMG were observed, and the therapeutic effect of electroacupuncture was evaluated.


## 3.2.5. Computer Image Analysis

The BX51 digital microscope camera system collects the images of each spinal cord section and magnifies them by 20 times. Under the same multiple, each section randomly selected three fields of vision, and the computer image analysis system was applied to semiquantitative analysis of the grayscale integral value of immune positive cells. The smaller the grayscale integral value, the stronger the tissue staining.


## 3.2.6. Statistical Analysis

The data were calculated by mean ± standard deviation. The standard of significance test isa = 0.05. SPSS11.5 was used for statistical analysis. In order to eliminate the influence of different basic discharges on the experimental results, the basic discharge amplitudes of young rats under the pressure of 20 mmHg, 40 mmHg, 60 mmHg, and 80 mmHgcrd were subtracted from the basic discharge amplitudes of young rats, and the difference represented the discharge amplitudes of different CRDs. Repeated ANOVA was used to analyze the AWR score and discharge data.


## 4. Results

According to the statistical analysis of the data, as shown in Figure3 and Table 2, with the increasing stimulation pressure, the AWR scores of the model group and the control group increased. In the range of 20–60 mmHg, the AWR score of the model rats was significantly higher than that of the control group (P<0.05), but there was no significant difference in 80 mmHg between the two groups. It suggested that visceral hyperalgesia appeared in the model rats.Figure 3
AWR score.Table 2
AWR score.
CRD pressure (mmHg)Control groupModel group200.61.8401.92.6602.73.2803.73.9According to the statistical analysis of the data, as shown in Figure4 and Table 3, with the increase of CRD pressure, the discharge amplitude of the external oblique muscle gradually increases. Under 20–80 mmHg CRD pressure, the discharge amplitude of the external oblique muscle of the model rats was significantly higher than that of the control group (P<0.05).Figure 4
Discharge detection of the external oblique muscle.Table 3
Discharge detection of the external oblique muscle.
CRD pressure (mmHg)Control groupModel group2036401117601625802736According to statistical analysis of the data, as shown in Figure5, different CRD pressure stimulation, at the same time, the AWR scores of model rats and normal control rats after electroacupuncture were compared. The results showed different CRD pressures (20–80 mmHg) (P<0.05). The results showed that multiple electroacupuncture had an obvious analgesic effect on the model rats, which could reduce visceral hyperalgesia and restore normal levels.Figure 5
Effect of electroacupuncture on visceral pain.According to the statistical analysis of the data, as shown in Figure6, the amplitude of the EMG of model rats was compared with that of the normal control rats after electroacupuncture. The results showed the pressure of 20–80 mmHg (P<0.05). The results showed that multiple electroacupuncture had an obvious analgesic effect in the model rats, which could reduce visceral hyperalgesia and recover to the normal level.Figure 6
The influence of electroacupuncture on EMG.


## 5. Discussion

At present, the pathophysiological process of IBS mainly includes gastrointestinal motility abnormality, visceral sensory disturbance, and gastrointestinal secretion abnormality. In all these pathophysiological processes, 5-hydroxytryptamine (5-HT) was found to be involved. 5-hydroxytryptamine (5-HT) is widely distributed in the peripheral and central nervous system. It is a monoamine with the indoleamine structure. 5-HT can affect its receptor, cause the changes of intestinal perception, movement and secretion in IBS patients, and produce various symptoms. According to modern medicine, there are not only pain centers but also tissue structures related to analgesia and regulation system in the central nervous system, which can integrate and process all kinds of stimulation information. Acupuncture can play an analgesic role through the integration of some central nerves, body fluids, and pain-regulating systems. The visceral fibers of the descending colon and rectum of the rats project from the pelvic nerve (parasympathetic nerve) to the l6-S2 spinal cord segment, and from the gastric nerve (sympathetic nerve) to the T13-L2 spinal cord segment. The dorsal horn of the spinal cord is the first relay station to transmit harmful information to the central nervous system. After the injury information is transmitted to the dorsal horn, the dorsal horn not only receives and transmits the injury information but also integrates the injury information. The 5-hydroxytryptamine in the spinal cord is derived mainly from the 5-hydroxytryptamine descending projection fiber in the brainstem. These fibers terminate in the dorsal horn of the spinal cord, release 5-hydroxytryptamine, act on receptors in the dorsal horn of the spinal cord, and play a role in pain regulation. There are many serotonin receptor subtypes in the dorsal horn of the spinal cord, which play an important role in the regulation of pain. As an important neurotransmitter, 5-HT2A plays an important role in the transmission and regulation of sensory information, especially nociceptive information at the spinal level. The 5-HT2A receptor plays an important role in the integration of pain information at the spinal level. 5-HT neurons in the brainstem are mainly concentrated in the raphe nucleus. The raphe nucleus group is not only an important mechanism of brain pain control but also a collection of 5-HT neurons, which can send up and down fibers. The ascending 5-HT fibers mainly come from the dorsal raphe nucleus and are distributed in the diencephalon, basal ganglia, and limbic system. Acupuncture information can activate neurons in the dorsal raphe nucleus and inhibit nociceptive neurons in the parafascicular nucleus of the thalamus. The descending 5-HT fibers mainly originate from the nucleus raphe magnus and descend to the spinal cord along the dorsolateral side of the spinal cord. The thalamus is not only an important relay station for transmitting nociceptive information to the cerebral cortex but also a complex analysis and synthesis center. The central central nucleus of the parafascicular nucleus and the plate nucleus is an important center for pain sensation and regulation. The cerebral cortex is the highest center of higher nervous activity, the center of conscious thinking, and the intelligent center of comprehensive reasoning and judgment.Acupuncture analgesia is not only a simple process of excitation and inhibition but also a complex regulatory process. It not only enhances the analgesic effect but also excessively suppresses the analgesic effect, which is in a dynamic balance. Xu Wei et al observed that peripheral nociceptive stimulation can activate neurons in the sensory cortex, and acupuncture information can also reach the cerebral cortex. The excitatory cortical somatosensory area II can inhibit the nociceptive responses of neurons in the central nucleus, parafascicular nucleus, and central lateral nucleus of the thalamus. However, in the block of somatosensory area II or the change of functional state of somatosensory area and aminobutyric acid II, the inhibitory effect of acupuncture on the pain response was not observed in the atomic nucleus, parafascicular nucleus, and central lateral nucleus of most central intermediate neurons, and it is suggested that the descending activity of the cerebral cortex is involved in the inhibition of pain transmission by acupuncture. Visceral hypersensitivity is related to the imbalance of neurotransmitter release and the increased sensitivity of sensory nerve endings to these media, which may involve many links such as receptors, signal afferent, spinal dorsal horn, and central nerve.; most of the afferent nerve fibers in the gastrointestinal tract are multimodal sensory nerve fibers, which can conduct various stimulation signals. According to histological markers, these fibers can be divided into two groups. One group contains calcitonin gene-related peptide and substance P (SP) and other neuropeptides. CGRP was mainly distributed in the visceral sensory nerve. 50% of sensory neurons containing CGRP also contain neurokinin. By regulating the expression of NKRL in primary afferent neurons of the spinal cord, visceral sensitivity increased. CGRP receptor antagonist can reduce the high sensitivity of colon. CGRP can cause visceral hypersensitivity. CGRP is involved in acupuncture analgesia. The gastrointestinal sensory nerve transmits the stimulation signal to the spinal cord, activates the mechanoreceptor of the primary afferent nerve of the spinal cord, then stimulates the spinal dorsal horn neurons to cause pain, and then transmits the signal to the brainstem. Acupuncture and moxibustion is based on the dialectical principle of “deficiency is tonic and essence is purgative.” Through the use of tonic, purgative, flat, purgative, and other techniques, the body’s own regulatory response can be achieved. From the perspective of traditional Chinese medicine theory, it is used to regulate meridians and collaterals, qi and blood, and Yin and Yang; from the perspective of modern life science, it plays a role by regulating the function of the neuroendocrine and immune system network. There are many endogenous bioactive substances involved in the change of acupuncture function, which is an active multilevel physiological regulation process.Nanotechnology is a new subject, which is devoted to the preparation of nanomaterials and the improvement of its practicability in various scientific fields. Metal-doped hybrid materials have been proved to be a drug for many pathogenic microorganisms and various cancers. Among all kinds of biomaterials, bio-based nanometals, including platinum, gold, silver, and their composites with graphene are becoming more and more important. In view of the new significance of metal biomaterials, our research focuses on the preparation of platinum, palladium, zinc oxide, and silver by using natural products as reducing agents and stabilizers of different plants. Second, these metals were loaded onto graphene oxide for clinical biological application. According to traditional Chinese medicine, the large intestine and lungs are located in the abdomen, the stomach meridian of the Foot Yangming, the spleen meridian of the foot Taiyin, and the meridians and collaterals of the Ren pulse. Therefore, abdominal pain caused by colorectal lesions includes abdominal pain caused by enteroscopy. According to the basic rules of the main treatment of the acupuncture points, the meridian of the acupuncture points such as the large intestine, the stomach meridian of Foot Yangming, the spleen meridian of Foot Taiyin, and the Ren meridian can be selected to relieve pain combined with the commonly used pain treatment methods. In addition to the local protection of intestinal mucosa, NOS can also be used as a reverse transcription information material of visceral sensory components to upload the information of intestinal injury to the relevant parts of the midbrain and spinal cord. According to the theory of somatic visceral convergence, the superficial dorsal horn of the spinal cord will rise along the thalamus tract of the spinal cord, and the gray matter around the central canal will be in the superficial dorsal horn, the medial lemniscus of the posterior line, and reaches the relevant brain area. In the process of nociceptive information transmission, the results of NOS detection are inconsistent, some experimental reports are up-regulated, and some experimental reports are down regulated. The expression of NOS positive neurons in PAG and DH increased after pain stimulation. Under the condition of noxious stimulation, NOS is involved in the transmission and regulation of noxious information at the level of spine and above. This may be due to the fact that in pain in spinal cord, the stimulation causes the release of Glu from the primary afferent terminal, the activation of NMDA receptor, the opening of receptor channels, coupled with the influx of Ca2+ and the assistance of calmodulin (CAM), substituting NADPH, catalyzing L-Arg, substituting NO, further activating guanosine cyclase, thus acting on the ion channel of cGMP, the regulation of phosphodiesterase (PDE) by CG liver, and the activation of spinal cord pain system. Many neurotransmitters work through NOS, and the excitatory amino acid NMDA can induce NO synthesis by activating NOS. By regulating the function of neuroendocrine system, acupuncture can improve the body’s defense and disease resistance; on the other hand, it is also one of the ways that acupuncture regulates the function of other organs. Generally speaking, acupuncture regulates the neuroendocrine system mainly through the hypothalamic pituitary system and also through the feedback of various neuroendocrine glands. All kinds of pressure and pain will cause over activation of multiple biological cascade systems, which will damage the body. E and NE are the main objective indexes reflecting the changes of neuroendocrine. The change of its content is one of the important indexes reflecting the stress response caused by harmful stimulation.


## 6. Conclusion

Electroacupuncture can significantly reduce the pain sensitivity of the model rats; electroacupuncture combined with the nerve growth factor can activate the proliferation, migration, differentiation, and integration of endogenous NSC and promote the regeneration and neurological function recovery after nerve injury. Acupuncture can reduce the visceral pain of colorectal distention by blocking the transmission of pain signals. Acupuncture can cause the changes of NOS, e, NE, and EK. The complex relationship between these neurotransmitters suggests that acupuncture may have a greater application value in improving and alleviating visceral pain due to colorectal swelling. The swelling visceral pain of colorectal in rats was relieved. The blood vessels and nerves in the body are accompanied by similar growth patterns. The activity and nutrition of blood vessels are regulated by nerves and their nutritional factors. NGF is a multifunctional peptide molecule. The amplitude of electromyogram of model rats and normal control rats after electroacupuncture were compared. The results showed the 2080 mmHg group is statistically significant (P<0.05). This shows that NGF promotes the proliferation, migration, and differentiation of endothelial tissue cells while reducing visceral hyperalgesia [26–34].



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*Source: 3755439-2022-10-14.xml*