Central Mechanisms Of Chronic Pain And Moxibustion-induced Analgesia In Patients With Knee Osteoarthritis:a Resting FMRI Study

Chronic pain involves different types of diseases.In clinical practice,in addition to traditional drug therapy,non-drug therapy is also an important alternative treatment.Acupuncture and moxibustion,as an essential means in the field of non-drug treatments,has been paid more and more attention in clinical practice.Knee osteoarthritis(KOA)is a common disease in clinic,often accompanied by chronic pain.At present,acupuncture and moxibustion are one of the main recommended treatment methods.Moxibustion refers to local warm stimulation in poticular acupoints.Our previous clinical practice and researches have confirmed that for patients with knee osteoarthritis,moxibustion treatment at the Dubi acupoint(or Wai Xi Yan,ST35)in the state of heat sensitization(the so called heat-sensitive moxibustion)has a better analgesic effects than that of the Dubi acupoint in the non-heat sensitization.The purpose of this study is to explore the central mechanisms of heat-sensitive moxibustion at Dubi acupoint(or Wai Xi Yan,ST35)on chronic pain in knee osteoarthritis patients by functional magnetic resonance technology.Scientific questions include:(1)How do activities in brain regions/central nuclei or their functional connections change in the chronic pain state in knee osteoarthritis patients?(2)Compared with normal control and the non-heat sensitive patients,how do the activities in the brain regions/central nuclei or their functional connectivity of the brain or nucleus change in patients with heat-sensitive knee osteoarthritis?In this study,70 KOA patients with chronic pain were enrolled.According to the heat sensation phenomena in the Dubi acupoint,35 patients were divided into the heat-sensitive group and 35 non-heat sensitive group,and 35 volunteers are used as control group matched by age and sex.We used the analysis methods of amplitude of low-frequency fluctuations(ALFF)and regional homogeneity(ReHo)in resting-state functional magnetic resonance imaging(R-fMRI)to study function activities and synchronization of the brain regions/nuclei in KOA patients with chronic pain in different states of heat sensitization and non-heat sensitization after moxibustion treatment.We also used region of interest(ROI)-based functional connectivity(FC)and graph theory-based degree centrality(DC)techniques to explore the characteristics of functional connectome.The main results are as follows:(1)Compared with those in the normal control group,the brain regions closely related to sensations and emotions showed higher and stronger actibation and functional connections in KOA patients with chronic pain:Increased ALFF values in the right lenticular putamen,right caudate nucleus,right hippocampus,right fusiform gyrus,right parahippocampal gyrus,and left inferior temporal gyrus,left middle temporal gyrus,left fusiform gyrus,left inferior occipital gyrus,and left supramarginal gyrus;Increased ReHo values in the right opercular inferior frontal gyrus,right insula,right rolandic operculum,right precentral gyrus,right superior temporal gyrus,triangular part of inferior frontal gyrus,and right fusiform gyrus,right inferior temporal gyrus,and left superior temporal gyrus,left rolandic operculum,the left cuneus;and the decreased ReHo values in the left opercular part of inferior frontal gyrus.The FC values was increased in the right precentral gyrus,and increased DC values in the right precentral gyrus and opercular part of inferior frontal gyrus.(2)In chronic pain patients with knee osteoarthritis,either moxibustion at non-heat-sensitive acupoints(non-heat-sensitive moxibustion)or moxibustion at heat-sensitive acupoints(heat-sensitive moxibustion)can change the functional activities and functional connections of different brain regions:After the acupoint non-heat-sensitive moxibustion,the ALFF values increased in the right middle frontal gyrus and the right opercular part of inferior frontal gyrus,the ReHo values increased in the right opercular part of inferior frontal gyrus,but the ReHo values decreased in right dorsolateral of superior frontal gyrus and left superior occipital gyrus.The DC values increased in the right inferior occipital gyrus.After the acupoint heat-sensitive moxibustion,the ALFF values increased in the right supramarginal gyrus/superior temporal gyrus,and lingual gyrus/limbic lobe,and inferior parietal lobule;the ReHo values increased in the right inferior parietal lobule/supramarginal gyrus,triangular part of inferior frontal gyrus,opercular part of inferior frontal gyrus,left caudate nucleus,left supramarginal gyrus,left opercular part of inferior frontal gyrus,left superior parietal gyrus,but the ReHo values decreased in the left superior temporal gyrus and middle temporal gyrus.The DC values increased in the left dorsolateral superior frontal gyrus was increased,but the DC values decreased in the left middle temporal gyrus/superior temporal gyrus and left putamen of lenticular nucleus.(3)In chronic pain patients with KOA,the heat-sensitive moxibustion enhanced the functional activities in more cognition-related brain regions than the non-heat sensitive moxibustion:ALFF values increased in the right orbital part of superior frontal gyrus,gyrus rectus,orbital part of middle frontal gyrus,right middle frontal gyrus,right dorsolateral of superior frontal gyrus,and left dorsolateral of superior frontal gyrus.But the ALFF values decreased in the left supramarginal gyrus.ReHo values increased in the left medial superior frontal gyrus,but the ReHo values decreased in the left median cingulate and paracingulate gyri/supplementary motor area,left thalamus,right lingual gyrus,left lingual gyrus,and left postcentral gyrus.The FC values decreased in the right middle frontal gyrus,right cuneus,left middle frontal gyrus and right middle occipital gyrus,and decreased DC values in the right postcentral gyrus and right superior temporal gyrus.In summary,①in chronic pain conditions in patients with KOA,the functional activities and functional connections are changed in multiple cortical brain regions related to sensations,emotions and cognitions,mainly including the occipital lobe(inferior occipital gyrus),temporal lobe(superior temporal gyrus/inferior temporal gyrus/middle temporal gyrus),medial nucleus of the thalamus and its projected marginal system(cingulate gyrus/insular lobe),prefrontal lobe.②Although both heat-sensitive moxibustion and non-heat-sensitive moxibustion can change the functional activities and functional connections of different brain regions,heat-sensitive moxibustion shows stronger effects through the increased activities of cognition-related frontal lobes(orbital part of superior/middle frontal gyrus-middle frontal gyrus-dorsolateral of superior frontal gyrus)and the decreased the functional connections of the limbic system(thalamus-lingual gyrus-postcentral gyrus).In this study,using R-fMRI-based analysis of functions of brain regions and their functional connections,the central mechanisms of chronic pain and moxibustion treatment for KOA patients were investigated.Functional activities and their functional connections of pain-related brain regions and the possible modulation of moxibustion on them during chronic pain treatment are complex that need further investigation.