Role of spinal CCR5 in remifentanil-induced hyperalgesia in rats with incisional pain

Objective To evaluate the role of spinal C-C motif chemokine receptor 5 (CCR5) in remifentanil-induced hyperalgesia in rats with incisional pain. Methods Thirty-two male Sprague-Dawley rats, weighing 240-260 g, aged 2-3 months, in which intrathecal and caudal catheters were successfully implanted, were divided into 4 groups (n=8 each) using a random number table: control group (group C), CCR5 antagonist maraviroc group (group M), remifentanil plus incisional pain group (group R+ I) and maraviroc plus remifentanil plus incisional pain group (group M+ R+ I). Phosphate buffer solution (PBS) 10 μl was intrathecally injected and normal saline was infused for 60 min at 1 μg·kg-1·min-1 via the caudal vein in group C. Maraviroc 100 pmol (in 10 μl of PBS) was intrathecally injected and normal saline was infused for 60 min at 1 μg·kg-1·min-1 via the caudal vein in group M. PBS 10 μl was intrathecally injected, then the model of incisional pain was established, and remifentanil 1 μg·kg-1·min-1 was infused for 60 min via the caudal vein in group R+ I.Maraviroc 100 pmol (in 10 μl of PBS) was intrathecally injected, then the model of incisional pain was established, and remifentanil 1 μg·kg-1·min-1 was infused for 60 min via the caudal vein in group M+ R+ I.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before infusion of remifentanil or normal saline (T0) and 2, 6, 24 and 48 h after stopping infusion (T1-4). The rats were sacrificed after the last measurement of pain threshold, and L4-6 segments of the spinal cord were removed for determination of the expression of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule-1 (Iba-1) by Western blot. Results Compared with group C, the MWT was significantly decreased and TWL was shortened at T1-4, and the expression of GFAP and Iba-1 in the spinal cord was up-regulated in R+ I and M+ R+ I groups (P 0.05). Compared with group R+ I, the MWT was significantly increased and TWL was prolonged at T1-4, and the expression of GFAP and Iba-1 in the spinal cord was down-regulated in group M+ R+ I (P<0.05). Conclusion Spinal CCR5 is involved in remifentanil-induced hyperalgesia in the rats with incisional pain, and the mechanism may be related to activating astrocytes and microglias. Key words: Piperidines; Hyperalgesia; Pain, postoperative; Receptors, CCR5; Spinal cord