A Study Of The Regulation Effect Of Acupuncture On The Resting-state Functional Connectivity Of Insula In Knee Osteoarthritis Patients

Objects:This study observed the changes of insula function network before and after acupuncture and celecoxib treatment on patients with KOA,in order to explore the partial central mechanism of acupuncture.Methods:1.The Pub Med,Web of Science,EMBASE,the Cochrane Library databases,China National Knowledge Infrastructure,Chongqing VIP,Wan Fang database and Chinese Biomedical Medical database were searched from January 2011 to June 2020.The literatures of acupuncture and moxibustion on KOA were be collected,screened and extracted to analyze the law of acupoints in KOA treatment by using Matlab and Apriori algorithm to provide reference for the acupoint prescription in the central mechanism study of acupuncture on KOA.2.Ninety-eight KOA patients and seventy-six HS were recruited in this study,all of them have received the f MRI scan.Based on the FC analysis,we chose the ventral frontal insula,the dorsal frontal insula,the middle insula,and the posterior insula as the regions of interest,investigated the differences in FC of insula between KOA patients and HS,in order to reference for the central mechanism study of acupuncture on KOA.3.Seventy-two KOA patients who met the inclusion criteria were randomly divided into the acupuncture group and celecoxib group.In the acupuncture group,patients received manual acupuncture treatment once a day for 2 weeks,10 sessions in total.In the celecoxib group,patients received 200 mg celecoxib orally per day for 2 weeks.VAS and WOMAC were used to evaluate the difference of therapeutic effect in the acupuncture group and celecoxib group before and after treatments.All patients have taken f MRI scans before and after treatments.Based on the FC analysis,we chose the four part of insula above as the regions of interest,investigated the differences of FC of insula before and after acupuncture and celecoxib treatments and between the two groups.Results:1.Totally 635 literatures were included.The top ten acupoints were: Dubi,Xiyan,Yanglingquan,Xuehai,Liangqiu,Zusanli,Yinlingquan,Ashi point,Heding,and Xiyangguan.The acupuncture and moxibustion treatment on KOA mainly selected acupoints along Foot-Yangming-Stomach Meridian and combined with proximal points around the knees.2.Characteristic of resting-state(rs)insula FC in patients with KOACompared with HS,the FC of insula-anterior cingulate cortex,middle cingulate cortex,frontal cortex,and postcentral gyrus in KOA patients were increased.Compared with HS,the FC of insula-posterior cingulate cortex and thalamus in KOA patients were decreased.The FC of insula-right middle frontal gyrus and bilateral postcentral gyrus were negatively related to the VAS score(r<-0.3,P<0.05);and the FC of insula-right superior frontal gyrus and right inferior frontal gyrus were positively related to the VAS score(r>0.3,P<0.05).3.Changes in rs-insula FC of patients with KOA in the acupuncture group and celecoxib group after treatments(1)The therapeutic effect of acupuncture and celecoxib on KOA patientsSixty-six KOA patients have completed this trial,including 33 patients in the acupuncture group and 33 patients in the celecoxib group.Within-group analysis: After treatments,the VAS,WOMAC(including pain,stiffness,and functional activity subscales),SAS,SDS scores of patients in acupuncture and celecoxib group significantly decreased(P<0.05),the SF-12 scores of patients in the two groups significantly increased(P<0.05),and the changes of VAS and WOMAC scores had clinically important differences.Between-group analysis: The VAS,WOMAC,SAS,SDS and SF-12 scores in patients between acupuncture and celecoxib groups after treatments showed no statistical difference(P>0.05).And the changes in these scores above in patients between acupuncture and celecoxib groups were non-significant(P>0.05).(2)Characteristic of rs-insula FC of the acupuncture treatment on KOA patientsAcupuncture group: After treatment,the FC of insula-anterior cingulate cortex(ACC),middle cingulate cortex(MCC),and frontal cortex were decreased.These altered FC brain regions were related to the changes of VAS scores after acupuncture treatment(r>0.3 or r<-0.3,P<0.05).Celecoxib group: After treatment,the FC of insula-postcentral gyrus and frontal cortex were decreased.And these changed FC brain regions were related to the changes of VAS scores after celecoxib treatment(r>0.3,P<0.05).Between-group analysis: Compared with the altered rs-insula FC of KOA patients in celecoxib group,the FC of insula-frontal cortex of KOA patients in acupuncture group were significantly decreased.Conclusions:1.Acupuncture and celecoxib can relieve pain,stiffness of KOA patients,regulate anxiety and depression,and improve their physical function and quality of life.2.KOA patients had significant changes of insula FC in ACC,MCC,frontal cortex,postcentral gyrus,thalamus,etc.when compared to HS.The mediation of insulaACC and frontal gyrus based on the brain network functions associated with cognitive control,attention and emotional regulation in pain may be the underlying partial mechanism of acupuncture treating for KOA.