Role of ERK signaling pathway in spinal cord in reduction of neuropathic pain by electro-acupuncture at Zusanli and Yanglingquan

Objective To investigate the role of ERK signaling pathway in spinal cord in reduction of neuropathic pain (NP) by electro-acupuncture (EA) at Zusanli and Yanglingquan.Methods Fifty male SpragueDawley rats,weighing 180-220 g,in which the intrathecal catheter was successfully placed without complications,were randomly divided into 5 groups (n =10 each):sham operation group (S group),chronic constrictive injury (CCI) group,acupuncture at acupoint group (EA group),acupuncture at non-acupoint group (NA-EA group),and ERK inhibitor U0126 group (U0126 group).NP was induced by CCI in groups CCI,EA,NA-EA and U0126.The animals were anesthetized with intraperitoneal chloral hydrate 300 mg/kg.The right sciatic nerve was exposed and 4 ligatures were placed on the sciatic nerve at 1 mm intervals.EA (intensity ＜ 1.5 mA,frequency 2Hz) of Zusanli and Yanglingquan lasting 30 min was performed once a day for 6 days starting from 4th day after induction of NP in group EA.EA was performed at the points 5 mm lateral to the acupoints of Zusanli and Yanglingquan on the operated side in group NA-EA.Intrathecal U0126 5 μg was started on 4th day after induction of NP twice a day for 6 consecutive days.The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured at 1 day before CCI (T0,baseline) and at days 3,5,7 and 9 after CCI (T1-4).The rats were sacrificed on 10th day after induction of NP and the right lumbar segment (L4-6) of the spinal cord was removed for determination of the expression of P2X3 receptor protein and mRNA,ERK1/2 and phosphorylated ERK1/2 (p-ERK1/2) in the spinal cord dorsal horn.Results Compared with group S,MWT was significantly decreased,TWL was significantly shortened,the expression of P2X3 receptor protein and mRNA,and p-ERK1/2 was up-regulated in the other 4 groups (P ＜ 0.01).Compared with CCI group,MWT was significantly increased,TWL was significantly prolenged,the expression of P2X3 receptor protein and mRNA,and p-ERK1/2 was downregulated in EA and U0126 groups (P ＜ 0.01),and no significant change in the parameters mentioned above was found in NA-EA group (P ＞ 0.05).Compared with EA group,MWT was significantly increased,TWL was significantly prolonged,the expression of P2X3 receptor protein and mRNA,and p-ERK1/2 was down-regulated in U0126 group (P ＜ 0.01).Conclusion ERK signaling pathway in spinal cord is involved in reduction of NP by EA at Zusanli and Yanglingquan. Key words: Mitogen-activated protein kinases; Electric stimulation therapy; POINT ST36 (ZUSANLI); POINT GB34 (YANGLINGQUAN); Neuralgia