Role of spinal ERK signaling pathway in reduction of remifentanil-induced hyperalgesia by electro-acupuncture at Zusanli in rats with incisional pain

Abstract

Objective To evaluate the role of spinal extracellular signal-regulated kinase (ERK) signaling pathway in reduction of remifentanil-induced hyperalgesia by electro-acupuncture (EA) at Zusanli in rats with incisional pain. Methods Fifty male adult Sprague-Dawley rats, weighing 250–280 g, in which the intrathecal catheter was successfully placed without complications, were randomly divided into 5 groups (n= 10 each) using a random number table: control group (group C), remifentanil + incisional pain group (group RI), EA at acupoint group (group E), EA at non-acupoint group (group NE), and 1/2 ERK inhibitor U0126 + EA at acupoint group (group UE). Normal saline 0.1 ml· kg–1· min–l was infused intravenously for 60 min in group C. In RI, E, NE and UE groups, after the model of incisional pain was established, remifentanil 1.0 μg · kg–1· min–l was infused for 60 min, and in addition, EA (intensity 10 mA, frequency 4 Hz) of Zusanli lasting for 60 min was performed at the same time in E and UE groups, and EA was performed at the points 5 mm lateral to the acupoints of Zusanli on the operated side simultaneously in group NE.ERK1/2 inhibitor U0126 5 μg (in 5% dimethyl sulfoxide 10 μl) was injected intrathecally in group UE, and 5% dimethyl sulfoxide 10 μl was injected intrathecally in the other groups.The mechanical paw withdrawal threshold (MWT) was measured before remifentanil or normal saline infusion (T1), and at 2 h, 1, and 2 days after the end of infusion (T2-4). After MWT was measured at T4, the expression of ERK1/2 and phosphorylated ERK1/2 (p-ERK1/2) in spinal cord dorsal horns was measured by Western blot. Results Compared with group C, the MWT was significantly decreased at T2-4 in RI, E, NE and UE groups, and the expression of p-ERK1/2 was up-regulated in RI, E and NE groups (P 0.05). Compared with group E, the MWT was significantly increased at T2-4, and the expression of p-ERK1/2 was down-regulated in group UE (P<0.05). Conclusion The mechaism by which EA at Zusanli reduces hyperalgesia induced by remifentanil in rats with incisional pain is related to inhibited activation of ERK signaling pathway in the spinal cord . Key words: Extracellular signal-regulated MAP kinases; Spinal cord; Electric stimulation therapy; POINT ST36 (ZUSANLI); Piperidines; Pain, postoperative; Hyperalgesia