Objective: To investigate whether analgesic effect of electroacupuncture(EA) is affected by p38 mitogen-activated protein kinase(p38 MAPK) on microglia. Methods: There were two experiments. The experiment 1: 40 male Sprague-Dawley(SD) rats were randomly divided into the normal, surgery, EA and sham EA groups, and the L5 spinal nerve ligation(SNL) on the right side was used to establish neuropathic pain model. EA was applied to bilateral Zusanli(ST36) and Kunlun(BL60) at 24, 48 and 72 h after SNL for 30 min, once per day. The paw withdrawal thresholds(PWTs) were measured before surgery(as base) and at 24, 25, 49 and 73 h after surgery. Phospho-p38 MAPK(p-p38 MAPK), oxycocin-42(OX-42, marker of microglia), and glial fibrillary acidic protein(GFAP, marker of astrocyte) in bilateral spinal cord dorsal horn(SCDH) were detected by immunofluorescence, respectively. The experiment 2: 40 male SD rats were cannulated for SNL-induced neuropathic pain, and then were randomly divided into the dimethyl sulfoxide(DMSO), EA plus DMSO, 4-(4-fluorophenyl)-2-(4-methylsulfonylpheny)-5-(4-pyridyl)-1H-imidazole(SB203580) and EA plus SB203580 groups. SB203580(30 nmol/L) was administered 5 min prior to EA treatment. The PWTs and OX-42 in bilateral SCDH were measured as mentioned above. Results: SNL-induced neuropathic pain reduced PWTs and increased the expression of p-p38 MAPK and OX-42 in bilateral lumbar SCDH of rats(P<0.01). Spinal p-p38 MAPK was only co-localized with OX-42 in our study. EA treatment significantly alleviated SNL-mediated mechanical hyperalgesia, and suppressed the expression of p-p38 MAPK and OX-42 in lumbar SCDH(P<0.05 or P<0.01). Intrathecal injection of low dose SB203580 had no influence on PWTs(P>0.05), but significantly inhibited the expression of OX-42 positive cells in bilateral SCDH(P<0.01 or P<0.05). EA plus SB203580 synergistically increased PWTs, and reduced the expression of bilateral spinal OX-42(P<0.01 or P<0.05). Conclusions: The central mechanism of EA-induced anti-hyperalgesia may be partially asso
