The Study Of Electroacupuncture On The Clinical Efficiency And Motor Cortical Excitability Mechanism For Postherpetic Neuralgia

ObjectivePostherpetic neuralgia(PHN)refers to the persistent pain at the lesion site after the elimination of the herpes zoster more than 3 months.It seriously affected the quality life of the patients,almost 50%of patients have poor response to the traditional analgesic drugs.Previous studies have shown that(1)the neuropathic pain diseases have been characterized by the recurrent attacks and associated with central sensitization,which caused the changes of the synaptic structures and function.These changes might induce long-term potentiation of synaptic transmission(one of the important mechanisms of memory formation),and ultimately leading to the change of central nervous system to produce“pain memory”;(2)electrical peripheral stimulation(EPS)has been proved that could regulate the brain plasticity involved in pain memory;(3)electroacupuncture(EA),as one of the methods of EPS,is an effective method for clinical treatment for chronic pain.EA as one of the effective treatment methods has been widely used to treat chronic pain.Furthermore,with the development of transcranial magnetic stimulation(TMS),it has been proved that TMS as safe and noninvasive technique has been widely used to evaluate the cortex excitability.Therefore,on the basis of meta-analysis to investigate the effect of EPS on brain plasticity,we systematically overviewed the mechanism of pain memory and explored the mechanism of EA on cortical plasticity of PHN through evaluating the EA efficacy on cortex excitability of PHN using TMS,and making a comparison between the patients and the healthy subjects.MethodsIn this study,the meta-analysis was registered on Prospero website(Registration N0.CRD420119121546),and the clinical research has been reviewed by the ethics committee of Guangdong Provincial Hospital of traditional Chinese medicine and registered on the clinical trial registration center.It is divided into three parts.First,meta-analysis was conducted on the regulatory effect of EPS on cortical plasticity in healthy subjects.Relevant studies were collected and evaluated from Pub Med,MEDLINE,EMBASE,Scopus,Web of Science and all Cochrane databases,etc.For the inclusion criteria,we included the randomized controlled trials or quasi-experimental studies that:a)enrolled healthy subjects;b)performed an electrical peripheral stimulation;c)assessed outcomes including motor-evoked potential amplitude(MEPs),motor threshold(MT),silent period,short-interval intracortical inhibition(SICI)and/or intracortical facilitation(SICF)with Transcranial magnetic stimulation(TMS).We assessed the risk of bias using the Minors tool.Hedge’s effect sizes of TMS responses and their 95%confidence intervals(95%CI)were calculated,and random-effects meta-analyses were performed.Second,using TMS to investigate the excitability of motor cortex wasconducted.20 PHN patients,18 healthy subject with right-handed were included in this study.Each subject underwent TMS and was investigated MEPs,motor threshold(MT),silent period,SICI and ICF with different TMS intensity.Independent sample t-test as one of statistical analysis has been used to analyze the difference between groups,and Pearson correlation has been used to analyze the correlation.Third,we investigated the clinical efficiency and mechanism of cortical plasticity for the EA on PHN.This study included 34 patients with chest PHN.This study conducted 2Hz EA and sham acupuncture as the interventions.We observed the clinical efficiency,including the pain scores(VAS),the sleep quality,pressure pain threshold,Short form pain scale(SF-MPQ),etc.Furthermore,we also used the TMS technology to monitor the exciting of motor cortex,including the resting movement threshold(RMT)and amplitude ratio of LTP effect which induced by PAS25 for PHN patients before and after treatment.The repeated measurement analysis of variance was used to explore the influence of the different treatment measures(EA and sham EA)over time(three scheduled time).Results(1)Thirty-one studies were included in the meta-analysis.We found a significant increase for MEPs in healthy subjects(P=0.000).The meta-analysis also showed that EPS application significantly increases SICF(P=0.000).Subgroup analysis showed that the efficacy of EPS is dependent on(i)EPS current density above motor threshold;(ii)EPS stimulation frequency less than or equal to 30Hz,and(iii)EPS with long duration more than 30mins.Effect sizes for the other outcome measures were not significant.(2)The results of second experiment included(i)comparing RMT on the motor cortex for the PHN group and healthy group respectively,the difference was statistically significant(P<0.05);(ii)there were no significant differences between the PHN group and control group for the MEPs and AMT.No significant differences were observed between the two groups with respect to SP(P>0.05);(iii)the results showed that there was a change of SICI in response on the patients with PHN under 70%stimulation intensity compared to controls(P<0.05).However,there was no significant difference between PHN patients and control in ICF(P>0.05);(iv)Pearson correlation analysis showed that the daily pain frequency of PHN patients was positively correlated with SICI(R~2=0.3244,P<0.05).RMT of contralateral cortex had no correlation with clinical pain related variables,which include the course of disease,pain intensity and pain frequency.(3)The results of the third experiment showed that(i)compared with the sham EA group,the VAS score of PHN patients was significantly reduced by 2Hz EA(P<0.05);(ii)SFMPQ-AS scores in the EA group after treatment and in the follow-up period were significantly lower than the scores before treatment,the difference was statistically significant(P<0.001);(iii)EA treatment can significantly improve the sleep quality of PHN patients,the difference was statistically significant(P>0.05).However,there was no significant change in pressure pain threshold before and after EA,and the difference was not statistically significant(P>0.05);(iv)EA treatment had no significant effect on the motor cortex threshold and MEPs on PHN patients(P>0.05);(v)Pearson correlation analysis was used to test the correlation between LTP plasticity of PAS25 and VAS during the treatment.We found that there was a significant correlation between LTP amplitude ratio and VAS scores(R~2=0.37,P=0.015<0.05).Conclusion(1)This meta-analysis provides evidence of EPS effects on cortical plasticity in healthy subjects.EPS including EA can significantly adjust the excitability of motor cortex,which is closely related to the stimulation intensity(above the motor threshold),the stimulation frequency(no more than30Hz)and the treatment duration(30-120mins).(2)The excitability of motor cortex for PHN subjects was hyperexcitability,which suggested that the increased excitability of the motor cortex might be one of the underlying mechanisms.(3)It has been proved that 2Hz EA has the clinical efficiency for the PHN patient’s life quality.Furthermore,it also could influence the cortical plasticity.Based on the correlation analysis,we speculated that the clinical efficiency of EA on PHN has related with the changes of brain plasticity.