Role of spinal COX-1 and COX-2 in remifentanil-induced hyperalgesia in mice with incisional pain

Objective To evaluate the role of spinal COX-1 and COX-2 in remifentanil-induced hyperalgesia in mice with incisional pain. Methods Thirty-two male C57BL/6J mice, aged 8-10 weeks, weighing 20-25 g, were divided into 4 groups (n=8 each) using a random number table method: control group (group C), incisional pain plus remifentanil group (group IR), incisional pain plus remifentanil plus selective COX-1 inhibitor group (group IR+ SC560), and incisional pain plus remifentanil plus selective COX-2 inhibitor group (group IR+ SC236). In IR, IR+ SC560 and IR+ SC236 groups, normal saline 10 μl, SC560 25 μg and SC236 25 μg were intrathecally injected, respectively, 15 min later remifentanil 10 μg/kg was injected via the tail vein for 4 times at 15 min intervals.An incisional pain model was established after the first injection of remifentanil.The mechanical paw withdrawal threshold (MWT) was measured at 24 h before normal saline or remifentanil injection and 3, 6, 24 and 48 h after the last injection (T0-T4). The mice were sacrificed after the last measurement of pain threshold, and the L4-6 segments of the spinal cord were removed for determination of the expression of COX-1 and COX-2 (by Western blot) and expression of COX-1 and COX-2 mRNA (by quantitative real-time polymerase chain reaction). Results Compared with group C, the MWT was significantly decreased, and the expression of COX-2 protein and mRNA was up-regulated in IR, IR+ SC560 and IR+ SC236 groups (P 0.05) .There was no significant difference in the expression of COX-2 protein and mRNA among group IR, group IR+ SC560 and group IR+ SC236 (P>0.05). There was no significant difference in the expression of COX-1 protein and mRNA among the four groups (P>0.05). Conclusion Compared with COX-1, spinal COX-2 plays a major role in the pathophysiological mechanism of remifentanil-induced hyperalgesia in mice with incisional pain. Key words: Prostaglandin-endoperoxide synthases; Piperidines; Pain, postoperative; Hyperalgesia