Objective:This study aimed to assess the effects of electroacupuncture(EA)at the contralateral,ipsilateral,or bilateral"Zusanli(ST36)"and"Yanglingquan(GB34)"on neuropathic pain caused by chronic contractile injury(CCI)and to explore the role of the nuclear factor erythroid 2-related factor 2(Nrf2)pathway in the effects of EA.Methods:Male Sprague-Dawley rats were subjected to the CCI model to induce neuropathic pain.A total of 45 rats were randomly divided into five groups(n=9):sham,CCI,EA-Co(CCI+EA at contralateral acupoints),EA-Ip(CCI+EA at ipsilateral acupoints),and EA-Bi(CCI+EA at bilateral acupoints).The rats received EA treatment on day 8 after CCI,once every alternate day,for a total of eight times.The time courses of mechanical pain threshold(MWT),hind paw withdrawal latency(HWL),and sciatic functional index(SFI)were determined.The expression levels of 8-hydroxydeoxyguanosine(8-OHdG),glutathione(GSH),superoxide dismutase(SOD)activity,interleukin-6(IL-6),interleukin-1 beta(IL-1β),and tumor necrosis factor factor-alpha(TNF-α)in the spinal cord were measured.The distribution of Nrf2,its expression of Nrf2 in both the cytosol and nucleus,and the protein levels of its downstream target genes,NQO1 and HO-1,were detected via double immunofluorescence staining and western blotting,respectively.Results:Following CCI,both MWT and HWL in the CCI group significantly decreased from day 14 after surgery(P<0.001).EA treatment exhibited significant antinociceptive effects induced by CCI by increasing the MWT and HWL values,especially bilateral EA(P<0.05).The SFI of the CCI group was significantly lower than that of the sham group(P<0.001).Only bilateral EA improved the SFI scores compared to the CCI group(P<0.05).8-OHdG levels in the spinal cord of the CCI group were significantly higher than those in the sham group(P<0.05),whereas GSH levels and SOD activity in the spinal cord of the CCI group were significantly lower than those in the sham group(P<0.001 and P<0.01,respectively).Bilateral EA administration significantl
