Effect and mechanism study on transcutaneous auricular vagus nerve stimulation for functional dyspepsia model rats

Objective:To explore the effect and its possible mechanism of the intervention of transcutaneous auricular vagus nerve stimulation(taVNS)for the functional dyspepsia(FD)model rats.Methods:Of the 25 male SD rats,6 rats were set as blank group,the other 19 rats were established to be the functional dyspepsia(FD)model by iodoacetamide intragastric administration,and 18 FD models were successfully established.The 18 model rats were randomly divided into a model group,a shamtaVNS group,and taVNS group,with 6 rats in each group.There was no intervention applied to the rats in the blank and model groups.Whereas,the rats in sham-taVNS group received stimulation to the rim of auricular concha of both sides,and those in taVNS group received stimulation to the cavity of auricular concha of both sides,for 30 min each time,once a day,7 days in succession.After the intervention,the gastric sensitivity of the rats in each group under different pressure conditions in the stomach,the expressions of serum brain-gut peptide motilin(MTL),cholecystokinin(CCK),glucagon-likepeptidel(GLP-1),and inflammatory factors IL-4,IL-10,and IL-1βwere detected.Results:(1)Gastric sensitivity:compared with the blank group,the gastric sensitivity of the model group was higher(P<0.05).Compared with the model group,the gastric sensitivity of the taVNS group was lower(P<0.05).Compared with the sham-taVNS group,the gastric sensitivity of the taVNS group was lower(P<0.05).(2)Expression of brain-gut peptide:compared with the blank group,MTL was lower,CCK and GLP-1 were higher in the model group(all P<0.05).Compared with the model group,MTL was higher,CCK and GLP-1 were lower in the taVNS group(all P<0.05).Compared with the shamtaVNS group,CCK and GLP-1 were lower in the taVNS group(both P<0.05).(3)Expression of inflammatory factors:compared with the blank group,IL-4 and IL-10 were lower and was higher in the model group(all P<0.05).Compared with the model group,IL-10 was higher and IL-1βwas lower in the shamtaVNS group(all P<0.05),while IL-4 and IL-10 were higher and IL-1βwas lower in the taVNS group(all P<0.05).Compared with the sham-taVNS group,IL-4 and IL-10 were higher and IL-1βwas lower in the taVNS group(all P<0.05).Conclusion:TaVNS can reduce the gastric sensitivity of FD model rats by peripheral anti-inflammatory action and regulating the abnormal secretion of brain-gut peptide.

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.

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.

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.