Neural mechanism of acupuncture-modulated gastric motility

AIM: To investigate the acupuncture-modulated gastric motility and its underlying neural mechanism.METHODS: Intragastric pressure and/or waves of gastric contraction in rats were recorded by intrapyloric balloon and changes of gastric motility induced by acupuncture stimulation were compared with the background activity before any stimulation. Gastro-vagal or splanchnic-sympathetic nerves were recorded or cut respectively for investigating the involvement of autonomic nerve pathways. Spinalization experiment was also performed.RESULTS: Acupuncture-stimulation by exciting Aδ and/or C afferent fibers, could only modulate gastric motility. Acupuncture-stimulation on fore- and hind-limbs evoked a moderate gastric motility followed by increased vagus discharges with unchanged sympathetic activity, while the same stimulus to the acupoints in abdomen resulted in reversed effects on gastric motility and autonomic nervous activities. The inhibitory gastric response was completely abolished by splanchnic denervation, but the facilitative gastric response to stimulation of acupoints in limbs was not influenced, which was opposite to the effect when vagotomy was performed. The similar depressive effects were produced by the stimulation at the acupoints homo-segmental to the gastric innervation in the animals with or without spinalization. However, the facilitation induced by the stimulation at the acupoints hetero-segmental to the gastric innervation was not observed in the spinalized animals.CONCLUSION: Facilitative effects of stimulating hetero-segmental acupoints are involved in the intact preparation of vagal nerves and spinal cord, while the inhibitory response induced by stimulating homo-segmental acupoints is involved in the intact preparation of sympathetic nerves. Only the acupuncture-stimulation with intensity over the threshold of Aδ and/or C afferent fibers can markedly modulate gastrointestinal motility.

Effective regularity in modulation on gastric motility induced by different acupoint stimulation

AIM： To investigate whether manual acupuncture at representative acupoints in different parts of the body can modulate responses of gastric motility in rats and regular effects in different acupoint stimulation. METHODS： The gastric motor activity of rats was recorded by the intrapyloric balloon. The changes of gastric motility induced by the stimulation were compared with the background activity in intragastric pressure and/or waves of gastric contraction recorded before any stimulation. Morphological study was also conducted by observing the Evans dye extravasation in the skin after mustard oil injection into the intragastric mucous membrane to certify cutaneous innervations of blue dots related to gastric segmental innervations. RESULTS： In all six rats that received mustard oil injections into intragastric mucosa, small blue dots appeared in the skin over the whole abdomen, but mainly in peri-midline upper- and middle- abdomen and middle-back, a few in thigh and groin. It may speculate that cutaneous innervations of blue dots have the same distribution as gastric segmental innervations. Acustimulation in acupoints of head-neck, four limbs, upper chest-dorsum and Iower-dorsum induced markedly augmentation of gastric motility （acupoints on headneck such as St-2： n = 16, 105.19 ± 1.36 vs 112.25 ± 2.02 and St-3： n = 14, 101.5 ± 1.75 vs 109.36 ± 1.8; acupoints on limbs such as Sp-6： n = 19, 100.74 ± 1.54 vs 110.26 ± 3.88; St-32： n = 17, 103.59 ± 1.64 vs 108.24 ± 2.41; St-36： n = 16, 104.81 ± 1.72 vs 110.81 ± 2.74 and U-11： n = 17, 106.47 ± 2.61 vs 114.77 ± 3.77, P 〈 0.05-0.001）. Vigorous inhibitory regulations of gastric motility induced by acu-stimulation applied in acupoints on whole abdomen and middle-dorsum were significantly different as compared with the controls before acu-stimulation （abdomen acupoints such as Cv-12： n = 11, 109.36 ± 2.09 vs 101 ± 2.21; Cv-6： n = 18, 104.39 ± 1.42 vs 91.83 ± 3.22 and St-21： n = 12, 107 ± 2.97 vs 98.58 ± 2.81; acupoints on middledorsum such as BI-17： n = 19, 100.63 ± 1.4 vs 92.21 ± 2.07 and BI-21： n = 19, 103.84 ± 1.48 vs 97.58 ± 2.16, P 〈 0.05-0.001）. CONCLUSION： Regular regulatory effects of facilitation and inhibition on gastric motility appear to be somatotopically organized in the acupoints of whole body, and the effective regularity of site-special acupoints on gastric motility is involved in segmental innervations between stomach and acupoints.

The mechanisms through which auricular vagus nerve stimulation protects against cerebral ischemia/reperfusion injury

Previous studies have shown that vagus nerve stimulation can improve patients' locomotor function.The stimulation of the auricular vagus nerve,which is the only superficial branch of the vagus nerve,may have similar effects to vagus nerve stimulation.However,the precise mechanisms remain poorly understood.In this study,rat models of cerebral ischemia/reperfusion injury were established by modified Longa ligation.Twenty-four hours later,7-day auricular vagus nerve stimulation was performed.The results showed that auricular vagus nerve stimulation promoted the secretion of acetylcholine,inhibited the secretion of interleukin-1β,interleukin-6,and tumor necrosis factor-α,and reduced connexin 43 phosphorylation in the ischemic penumbra and motor cortex,promoting locomotor function recovery in rats with cerebral ischemia/reperfusion injury.These findings suggested that auricular vagus nerve stimulation promotes the recovery of locomotor function in rats with cerebral ischemia/reperfusion injury by altering the secretion of acetylcholine and inflammatory factors and the phosphorylation of connexin 43.This study was approved by the Animal Use and Management Committee of Shanghai University of Traditional Chinese Medicine on November 8,2019(approval No.PZSHUTCM191108014).

经皮耳迷走神经刺激:临床应用与机制

Vagus nerve stimulation(VNS)has been recognized by the U.S.Food and Drug Administration(FDA)as an effective alternative therapy for a wide range of diseases.However,its application is hampered by a variety of issues,including high surgical risks and the long-term presence of a foreign body within the patient.Transcutaneous auricular vagus nerve stimulation(tavNs)has emerged as a non-invasive,low-cost method developed from VNS,aiming to replace surgically implanted VNS for the treatment of disease.Unlike traditional acupuncture,tavNS can be selfadministered by patients wherever possible,with a non-invasive nature and easy acceptability for patients.Compared with other auricular points,tavNS can regulate the function of internal organs by stimulating the auricular points that represent different organs.Initially,tavNS was only considered an alternative therapy to VNS for the treatment of epilepsy.However,its application has now been extended to several other diseases,including central nervous system disorders,peripheral cardiovascular diseases。

Transcutaneous Auricular Vagus Nerve Stimulation: From Concept to Application

Whether in the West or the East,the connection between the ear and the rest of the body has been explored for a long time.Especially in the past century or more,the relevant theoretical and applied research on the ear has greatly promoted the development of ear therapy,and finally the concept of transcutaneous auricular vagus nerve stimulation(taVNS)has been proposed.The purpose of taVNS is to treat a disease non-invasively by applying electrical current to the cutaneous receptive field formed by the auricular branch of the vagus nerve in the outer ear.In the past two decades,taVNS has been a topic of basic,clinical,and transformation research.It has been applied as an alternative to drug treatment for a variety of diseases.Based on the rapid understanding of the application of taVNS to human health and disease,some limitations in the development of this field have also been gradually exposed.Here,we comprehensively review the origin and research status of the field.

Effect of transcutaneous auricular vagus nerve stimulation on fasting blood glucose and serum insulin concentration in Zucker diabetes fatty rats

Objective:To observe the influence of transcutaneous auricular vagus nerve stimulation(taVNS) on fasting plasma glucose(FPG) and serum insulin(INS) in Zucker diabetes fatty(ZDF) rats and explore the regulatory effect of taVNS on blood glucose in ZDF rats.Methods:A total of 20 male ZDF rats were randomized into a model group and a taVNS group,10 rats in each one.Besides,the other 10 Zucker Lean(ZL) rats were selected to be a control group.The rats in the control group were fed with common forage and those in the model group and the taVNS group were fed with high-sugar and high-fat forage.The intervention of electric stimulation was applied in the rats of taVNS group,with 2/15 Hz in frequency,disperse-dense wave and 2 mA in intensity.Each intervention lasted 30 min,once a day,consecutively for 12 weeks.No any intervention was given in the control group and the model group.The body mass and FPG level were recorded once every 2 weeks in the rats.After the experiment,the rats were sacrificed and blood sample was collected.Enzyme linked immunosorbent assay(ELISA) was adopted to determine the level of serum INS in the rats.Results:After the modeling,compared with the control group,the body mass and FPG level were all higher(P <0.05,P <0.01) and the concentration of serum INS was lower(P <0.01) in the rats of the model group.After intervention,compared with the model group,the body mass was lower in week 6 to 10(P <0.01,P <0.05),FPG level was lower in week 8 to 12(P <0.01,P <0.05) and serum INS concentration was higher(P <0.01) in the rats of the taVNS group.Conclusion:TaVNS apparently improves in hyperglycemia in ZDF rats and increases serum insulin concentration in the rats.

Systematic review and meta-analysis of the therapeutic effect on functional dyspepsia treated with acupuncture and electroacupuncture

Objective:To review systematically the therapeutic effect and safety of acupuncture or electroacupuncture(EA)on functional dyspepsia(FD).Methods:Using computer,the randomized controlled trials(RCTs)of FD treated with acupuncture or EA were retrieved from the databases,i.e.Cochrane Library,PubMed,EMbase and Web of science,from the date of database establishment to June 1,2020.Using the assessment tool of risk of bias in Cochrane Handbook for systematic reviews of interventions,5.1.0,the quality of the included RCTs were evaluated in methodology.Meta-analysis was performed by RevMan 5.3 software.Results:A total of 10 articles were included,with 1202 cases involved.In this study,the effectiveness of EA or acupuncture on FD was analyzed in comparison with the treatment with sham-acupuncture,sham-EA or western medication.The results indicated that compared with sham-acupuncture or shamEA,acupuncture or EA greatly relieved the clinical symptoms of FD(SMD=-3.03,95%Cl[-3.56,-2.50],P<0.00001)and obtained a higher clinical response rate(OR=5.09,95%CI[3.30,7.86],P<0.00001),but the difference was not significant statistically in gastric electrical activity(P>0.05).Compared with gastric prokinetics,acupuncture or EA more effectively reduced the symptom score(MD=-3.03,95%CI[-3.56,-2.50],P=0.02),but the differences were not significant in the aspects of the improvement of clinical effective rate(OR=1.33,95%CI[0.70,2.52],P=0.39),the promotion of gastric half-emptying(MD=0.23,95%Cl[-1.94,2.40],12=0%,P=0.83),the promotion of motilin secretion(SMD=-0.06,95%CI[-0.23,0.11],I^(2)=0%,P=0.50)and the increase of gastric electrical activity(MD=-0.01,95%Cl[-0.03,0.01],I^(2)=0%,P=0.41).The three RCT studies with adverse events reported indicated that the difference in the incidence of the adverse events was not significant statistically in comparison of acupuncture with sham-acupuncture or gastric prokinetic agent(P<0.05).Conclusion:Regarding the improvement in the symptoms of FD,the effect of EA or acupuncture is superior to the sham-acupuncture group or the western medication group.Simultaneously,the clinical response rate in the treatment with EA or acupuncture is higher than the sham-acupuncture group.During the treatment with EA,some adverse reactions happened in treatment of FD with acupuncture or western medication.Even though there are the limitations in quality and quantity of the included trials,EA and acupuncture still deserve to be promoted in treatment of FD.However,more studies of RCTs with largescale sample,high quality and multiple centers are required for a further verification of the therapeutic effect.

Transcutaneous auricular vagus nerve stimulation for functional dyspepsia:A randomized controlled trial

Objectives:To observe the clinical long-term therapeutic effect on functional dyspepsia(FD) in the comparative study of transcutaneous auricular vagus nerve stimulation(taVNS) with transcutaneous auricular none-vagus nerve stimulation(tnVNS).Methods:A total of 90 FD patients were randomized into a taVNS group and a tnVNS group,45 cases in each one.The patients in both the taNVS group and the tnVNS group were treated 5 times a week,30 min each time,for 4 weeks totally.Before treatment,after treatment and in follow-up visit,overall symptom points,functional dyspepsia-related quality of life questionnaire(FDQOL),Hamilton anxiety scale(HAMA),Hamilton depression scale(HAMD) and self-rating depression scale(SDS) were adopted to evaluate the severity of the symptoms and observe the clinical therapeutic effect of patients.Results:Compared with the scores before treatment,the overall symptom points,FDDQL,HAMA,HAMD and SDS at each time point after treatment were all lower in the patients of the taVNS group.The scores of FDDQL after treatment were almost all higher than that before treatment in the self-comparison of each group.All of the above differences were significant statistically(all P <0.05).Compared with the tnVNS group,the overall symptom points,FDDQL, HAMA,HAMD and SDS at each time point after treatment were all lower in the taVNS group and the score of FDDQL was higher,indicating the statistical differences(all P<0.05).Conclusion:Transcutaneous auricular vagus nerve stimulation is applicable for the treatment of functional dyspepsia.Compared with the control group,taVNS obtains a better long-term effect.

Transcutaneous auricular vagus nerve stimulation for impaired glucose tolerance:a randomized controlled trial Protocol

Background:impaired glucose tolerance(IGT)is the early stage of diabetes and it would be deteriorated to type 2 diabetes mellitus(T2 DM)easily if no intervention provided.In western medicine,drug therapy assisted with the intervention of lifestyle is predominated.However,drug therapy brings serious side effect and high prices,while lifestyle intervention is difficult to be insisted on by patients.Therefore,a green and effective intervention mode is urgently needed.Transcutaneous auricular vagus nerve stimulation(taVNS)is a noninvasive and green therapeutic method based on the theory of traditional Chinese medicine(TCM),which can regulate glucose metabolism and reduce blood glucose,but the clinical effect of it has not been clarified yet at present.Hence,this randomized controlled trial(RCT)aims at exploring the effectiveness and safety of taVNS in the treatment of IGT.Methods:a total of 158 patients with IGT will be randomized into a taVNS group and a transcutaneous non-auricular vagus nerve stimulation(tnVNS)group,79 cases in each one.In the taVNS group and the tnVNS group,electric stimulation would be applied to Yidan(胰胆pancreas and gallbladder,CO11)and Pi(脾spleen,CO13)on auricular concha and Jian(肩shoulder SF4,5)on auricular rim respectively.The electric stimulation parameters would be the same in the patients of two groups,for 30 min in each treatment,twice a day,6 weeks as one course and 2 courses of treatment required totally.In week 0,6 and 12 of intervention,the effectiveness indicators would be determined,i.e.fasting plasma glucose(FPG),2 h plasma glucose(2 hPG)and glycosylated hemoglobin(HbA1c)successively.On week 0 and 12,body mass index(BMI)would be calculated,respiration,pulse and blood pressure would be recorded separately.Discussion:through observing the regulatory effect of taVNS on FPG,2 hPG,HbAlc and BMI as well as the adverse reactions,the effectiveness and safety of taVNS in treatment of IGT would be evaluated.This study will provide a safe,effective,convenient and nontoxic side effect intervention for clinical treatment of IGT and prevention from the occurrence and development of T2DM.

Effects of transcutaneous auricular vagus nerve stimulation on intestinal ligandins in a rat model of functional dyspepsia

Objective:Transcutaneous auricular vagus nerve stimulation(taVNS) can relieve the symptoms of functional dyspepsia(FD) and improve the quality of life of patients,however,the mechanism underlying this effect remains unclear.Therefore,this study aimed to investigate the effects of taVNS on the expression of intestinal mucosal ligandins.Methods:This study was conducted on 24 specific Spathogen-free Sprague-Dawley rats(12 males and12 females).The rat model of FD was established by tail-clip stimulation.After FD was established successfully,all rats were randomized to either the normal group(n=6),model group(n=6),taVNS group(n=6),or sham-taVNS group(n=6).After two weeks of the respective intervention,the score of their general conditions,3 h food intake,gastric emptying rate,and the histology of gastric antrum tissues were observed to evaluate modeling success,and then the effect of taVNS was evaluated.Western blotting was used to assess the expression of the tight junction ligandins-ZO-1 and occludin-and the adhesion ligandin-β-catenin-in the duodenum.The effect of taVNs on the expression of intestinal mucosal barrier ligandins-ZO-1,occludin,and β-catenin-in FD rats was preliminarily investigated.Results:When the model-induced period was finished,the manifestations of FD in the model group rats were mental exhaustion,reduced activities,decreased score of the general conditions,and decreased3 h food intake,compared to the normal group rats.In addition,minimal eosinophil infiltration,without any mucosal erosion or ulcer,was observed in the gastric antrum mucosa.At the end of the study,the mental state of the FD rats improved,and their activities and gastric emptying rate increased in the taVNS group rats.Compared to the normal rats,the duodenal mucosa had less expression of the tight junction ligandins ZO-1 and occludin,but β-catenin expression remained unchangedin the model rats.The expression of the tight junction ligandins ZO-1 and occludin were increased in the duodenal mucosa of model rats after the taVNS intervention.Conclusion:TaVNS can improve the gastric motility and mental state of rats with FD.It may play a therapeutic role by improving the expression of the tight junction ligandin ZO-1 and occludin in the duodenal mucosa,while also repairing the duodenal mucosal barrier.

Auricular concha eletroacupuncture modulates lipid-lipoprotein metabolism in rats submitted to cold stress

Objective:To explore whether auricular concha eletroacupuncture(ACEA)is effective in regulating lipidlipoprotein metabolism in rats submitted to cold stress.Methods:Thirty-six adult male Sprague-Dawley rats were placed in four groups(9 rats in each group),the rats in three groups of which were submitted to cold stress for fourteen days,the last one of which was a control group.After the cold stress process,in those three groups,the rats of one group were with no treatment(stress only),two were treated with either ACEA or auricular margin eletroacupuncture(AMEA)repeated for fourteen days.On the 14th day,all the rats were sacrificed after all experimental procedure for blood sampling.Blood glucose,triglycerides(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)levels were tested by using the collected serum.Plasma lecithin-cholesterol acyltransferase(LCAT)was measured with ELISA kit.Results:ACEA down-regulated the TG level(P<0.05)and LDL-C level(P<0.05),and up-regulated HDL-C level(P<0.05)and LACT level(P<0.05).AMEA did not regulate the bio-markers.Conclusion:ACEA played an important role in regulating lipid-lipoprotein metabolism in rats submitted to cold stress.

Application of Photobiomodulation Therapy in Acupuncture

Photobiomodulation(PBM)therapy is a therapeutic method that can produce a range of physiological effects in cells and tissues using certain wavelengths.The reparative benefits of PBM therapy include wound healing,bone regeneration,pain reduction,and the mitigation of inflammation.Advances in the development of laser instruments,including the use of high-intensity lasers in physiotherapy,have recently led to controllable photothermal and photomechanical treatments that enable therapeutic effects to be obtained without damaging tissue.The combination of PBM therapy with acupuncture may provide new perspectives for investigating the underlying therapeutic mechanisms of acupuncture and promote its widespread application.

Medulla Oblongata Mechanism of Inhibitory Effect of Thermal Stimulation to Nociceptive Colorectal Distention in Rats

Objective: To discuss mechanism of moxibustion(thermal stimulation) effect and best moxibustion stimulus parameter.Methods: Experiments were performed on 48 male Sprague-Dawley rats. Unit discharges from individual single neuron were recorded extracellularly with glass-microelectrode in Subnucleus Reticularis Dorsalis(SRD). Visceral-intrusive stimulation is done by colorectal distension. Thermal stimulation with different temperature(40°C, 42°C, 44°C, 46°C, 48°C, 50°C, 52°C) and different stimulus area(diameter of circle : 1.0 cm, 1.5 cm, 2.0 cm, 2.5 cm, 3.0 cm, 3.5 cm, 4.0 cm) was applied around RN12 during nociceptive colorectal distension.Results: SRD neurons could be activated by visceral stimulation within noxious range. Under low temperature of stimulus, especially under45°C of pain threshold to ordinary people, visceral nociceptive afferent facilitated thermal stimulus from the body surface. While after thermal stimulation reached a harmful degree, the thermal stimulus will inhibit visceral nociceptive afferent. Moreover, statistics show that the higher the temperature is, the smaller the size of stimulation area is needed, and they correlate with each other negatively.Conclusion: Visceral nociception could be inhibited by somatic thermal stimulation with specific parameter at medulla level. According to our finding, best thermal stimulation temperature is around 48°C and the best size of stimulation area is around 3.14-7.07 cm2(with 2.0-3.0 cm diameter).