The Effects And Underlying Mechanism Of Electroacupuncture On Peripheral Nerve Injury Induced Neuropathic Pain And Postoperative Cognitive Dysfunction

ObjectivesNeuropathic pain and postoperative cognitive dysfunction,with high incidence,profoundly affect the life quality and mortality of patients.The pathogenesis of neuropathic pain and postoperative cognitive dysfunction have not been fully elucidated,resulting in the lack of better preventive measures and treatments.Acupuncture is one of the traditional Chinese medical treatment methods,which has potent effect on pain and nervous system diseases,but the mechanism of acupuncture remains unclear.Therefore,this study attempts to explore the effects and underlying mechanism of electroacupuncture on peripheral nerve injury induced neuropathic pain and postoperative cognitive dysfunction.MethodsAdult mice(aged 6-8 weeks)were used to establish a chronic sciatic nerve constriction model,and electroacupuncture was performed for 7consecutive days starting 1 day after surgery.Paw withdrawal threshold,inflammatory factors,ATP content and ATP hydrolases were measured in dorsal root ganglion.After identified the changes of PAP in DRG,PAP was specifically knocked down,and the indexes mentioned above was determined again.DRG neurons were cultured in vitro and treated with an endocytosis inhibitor to detect the protein abundance and m RNA expression level of PAP.Co-immunoprecipitation was used to detect the interaction between PAP and AP2 protein.Detect the phosphorylation of AP2.Eighteen months old mice were selected to establish the POCD model after tibial fracture internal fixation.Electroacupuncture was performed 1day before and 2 days after surgery.Reference memory was detected by Morris water maze and the changes of central immune cells were detected by immunofluorescence.Adult mice(aged 6-8 weeks)underwent multiple anesthesia/surgery,after that reference memory detect was detected by Morris water maze,central nervous system inflammation and changes in cholinergic markers were investigated.ResultsThe Von Frey test results showed that the hind paw withdrawal threshold of the electroacupuncture group was significantly increased,and the ATP content in the dorsal root ganglion was significantly reduced.After electroacupuncture treatment,the fluorescence signal of satellite glial cells and microglia decreased significantly,and the PAP expression was increased.After the specific knockdown of PAP in DRG,the hind paw withdrawal threshold of the knockdown group was significantly lower than that of the control group,and the fluorescence signals of satellite glial cells and microglia also increased.PAP protein content was significantly increased after treated with endocytosis inhibitor,and co-immunoprecipitation results showed that there was a protein interaction between PAP and AP2.EA treatment promotes the dephosphorylation of AP2,and CO-IP showed the interaction between PAP and AP2 M subsided.Morris water maze showed that there was no significant difference in the latency and the preference for the target quadrant between the surgery group and the electroacupuncture group.Compared with the control group,the multiple anesthesia/surgery group had no significant difference in the latency and the preference for the target quadrant.ConclusionsCCI surgery induced tactile analgesia in adult mice,accompanied by the increase of extracellular ATP and the decrease of ecto-nucleotidase prostatic acid phosphatase in DRG.EA treatment increased the abundance of PAP and promote the hydrolysis of extracellular ATP by promoting the phosphorylation of AP2 M,thus alleviated the tactile analgesia of CCI mice.Electroacupuncture did not affect reference memory of aged mice after tibial fracture internal fixation.Multiple anesthesia/surgery does not impair spatial reference memory in young adult mice.