Role of spinal protein kinase C in remifentanil-induced hyperalgesia in rats with incisional pain: the relationship with phosphorylation of NR1

Abstract

Objective To evaluate the role of spinal protein kinase C(PKC)in remifentanil-induced hyperalgesia in rats with incisional pain and the relationship with phosphorylation of R1 subunit-containing NMDA receptor(NR1). Methods Sixty SPF adult male Sprague-Dawley rats, weighing 220–250 g, were randomly divided into 5 groups(n=12 each)using a random number table: control group(group C), incisional pain group(group I), remifentanil group(group R), Go7874 + incisional pain group(group G), and Go7874 + remifentanil group(group G+ R). Incisional pain was induced by an incision made into the plantar surface of the right hindpaw of anesthetized rats in I, R, G and G+ R groups except group C. In addition, remifentanil(0.04 mg/kg, remifentanil 1 mg in 40 ml of normal saline)was infused subcutaneously over 30 min during operation in R and G+ R groups, PKC inhibitor Go7874 10 μl(12.5 nmol, in 10 μl of 10% dimethyl sulfoxide)were intrathecally injected at 30 min before operation in G and G+ R groups, and 10% dimethyl sulfoxide 10 μl was intrathecally injected in the other groups.The mechanical paw withdrawal threshold(MWT)and thermal paw withdrawal latency(TWL)were measured at 24 h before operation and 2, 6, 24 and 48 h after operation(T0-4). At 24 h after operation, 3 rats in each group were sacrificed, and the L3-5 lumbar segment of the spinal cord was removed for determination of the phosphorylated NR1(p-NR1)expression in the dorsal horn on the right side using Western blot. Results Compared with group C, the MWT was significantly decreased, and TWL was shortened at T1-4 in I, R and G+ R groups, and at T3, 4 in group G, and the expression of p-NR1 was up-regulated at T3 in I, R, G and G+ R groups(P<0.05). Compared with group I, the MWT was significantly decreased, and TWL was shortened at T1-4 in group R, the MWT was increased, and TWL was prolonged at T1-4 in group G, the MWT was increased at T3, 4, and TWL was prolonged at T1-4 in group G+ R, the expression of p-NR1 was up-regulated at T3 in group R, and the expression of p-NR1 was down-regulated at T3 in G and G+ R groups(P<0.05). Compared with group R, the MWT was significantly increased, and TWL was prolonged at T1-4, and the expression of p-NR1 was down-regulated at T3 in group G+ R(P<0.05). Conclusion Spinal PKC is involved in remifentanil-induced hyperalgesia in rats with incisional pain, which is related to decrease in the phosphorylation of NR1. Key words: Protein kinase C; Spinal cord; Piperidines; Pain, postoperative; Hyperalgesia; Receptors, N-methyl-D-aspartate