The Analgesic Mechanism Of Electroacupuncture Treatment Of Chronic Neuralgia Based On High Mobility Group Box 1 Signaling Pathway In Hippocampus And Amygdala

Objective : To observe the therapeutic effect of electroacupuncture on rats with neuropathic pain,and to confirm that its therapeutic effect is achieved by down-regulating the high mobility group protein(HMGB1)in the rat brain and its downstream cytokine levels.Methods: Thirty-six male Sprague-Dawley rats were randomly divided into sham operation group,model group and electroacupuncture(EA)group,12 rats/group.Rats in the model group and the EA group underwent sciatic nerve ligation(CCI)in the left hind limb to simulate neuropathic pain.Rats in the sham-operated group were not ligated after separation of the nerves.EA group rats were given daily EA intervention from the 8th day after surgery for 7 consecutive days.The mechanical withdrawal threshold(WMT)of the rats in each group were measured 1 day before surgery,7 days after surgery,10 days after surgery and 14 days after surgery.The rats were sacrificed on the 15 th day.The levels of TNF-? and IL-1? in hippocampus and amygdala were detected by ELISA.The m RNA levels of toll-like receptor 4(Tlr4R)and advanced glycation end products AGEs(Ager)were detected by real-time PCR.The HMGB1 gene and protein levels were detected by real-time PCR and Western blot.Results:(1)The MWT values of rats in the EA group and the model group were significantly lower than those in the sham-operated group(P < 0.001).After EA intervention,the MWT values of the rats in the EA group were higher than those in the model group(P < 0.05,P < 0.01);(2)The levels of TNF-? and IL-1? in the hippocampus and amygdala of the model group were significantly higher than those in the sham-operated group(P < 0.001).The levels of TNF-? and IL-1? in the hippocampus and amygdala of rats in the EA group were lower than those in the model group(P < 0.05).(3)The m RNA expression levels of HMGB1,Tlr4 R,and Ager in the hippocampus and amygdala of the model group were significantly increased compared with the sham-operation group(P < 0.001).The m RNA expression levels of HMGB1,Tlr4 R,and Ager in the hippocampus and amygdala of the EA group were lower than those in the model group(P < 0.001).(4)The expression levels of HMGB1 protein in the hippocampus and amygdala of the model group were significantly increased compared with the sham-operation group(P < 0.001),and significantly down-regulated in the EA group relevant to the model group(P < 0.05).Conclusion: EA intervention has a certain therapeutic effect on NPP,and this therapeutic effect may be achieved by inhibiting the expression of HMGB1 in rat hippocampus and amygdale,and down-regulating the levels of downstream TNF-? and IL-1?.