Changes in CCL3 and CCR5 expression in spinal cord during hyperalgesia induced by remifentanil in rats with incisional pain

Objective To evaluate the changes in the expression of CC-chemokine ligand 3(CCL3)and CC-chemokine receptor 5(CCR5)in the spinal cord during hyperalgesia induced by remifentanil in rats with incisional pain. Methods Thirty-two male Sprague-Dawley rats, aged 2-3 months, weighing 240-260 g, were randomly divided into 4 groups(n=8 each)using a random number table: control group(group C), incisional pain group(group I), remifentanil group(group R)and remifentanil+ incisional pain group(group R+ I). A 1-cm longitudinal incision was made in the plantar surface of the left hindpaw in anesthetized rats.While the model of incisional pain was established, remifentanil was infused for 60 min at 1 μg·kg-1·min-1.At 24 h before infusion of remifentanil(baseline)and 2, 6, 24 and 48 h after the end of infusion, the mechanical paw withdrawal threshold(MWT)and thermal paw withdrawal latency(TWL)were measured.The rats were sacrificed after the last measurement of pain threshold, the lumbar segment(L4-6)of the spinal cord was removed for determination of CL3 and CCR5 mRNA expression(by real-time PCR)and CL3 and CCR5 expression(by Western blot). Results Compared with group C, the MWT was significantly decreased, the TWL was shortened, and the expression of CCL3 and CCR5 mRNA and protein was up-regulated in I, R and R+ I groups.Compared with I and R groups, the MWT was significantly decreased, the TWL was shortened, and the expression of CCL3 and CCR5 mRNA and protein was up-regulated in group R+ I. Conclusion The mechanism by which remifentanil induces hyperalgesia is related to up-regulated expression of CCL3 and CCR5 in the spinal cord of rats with incisional pain. Key words: Piperidines; Hyperalgesia; Pain; Chemokine CCL3; Receptors, CCR5; Spinal cord