Involvement of Spinal CCL2 in Remifentanil-induced Hyperalgesia in Rats / 中山大学学报(医学科学版)

ABSTRACT

remifentanil；hyperalgesia；CCL2；microglia@#【Objective】To observe C-C motif chemokine ligand 2（CCL2）mediates remifentanil-induced hyperalgesia by activating microglia in rats.【Methods】Thirty-six adult male SD rats were equally and randomly divided into 6 group with 6 rats in each group：normal saline ，remifentanil，saline + intrathecal injection of phosphate buffer saline（PBS）， remifentanil + intrathecal injection of PBS，saline + intrathecal injection of CCL2 neutralizing antibody and remifentanil + CCL2 neutralizing antibody. To establish remifentanil-induced hyperalgesia model，remifentanil［4 μg/ （kg·min）2 h］ was continuously infused into rats via the tail vein. Then ，immunofluorescence and western blot were performed to examine the expression of spinal CCL2 in rats. Thirty minutes before remifentanil infusion，intrathecal injection of CCL2 neutralizing antibody was performed to observe remifentanil-induced hyperalgesia and the effect on the activation of microglial in the spinal cord of rats.【Results】Compared with the normal saline group，the thermal and mechanical pain thresholds in the remifentanil group were significantly reduced（P < 0.05）. The expression of protein（0.66 ± 0.071 vs. 0.18 ± 0.04；P < 0.001）and average immunofluorescence density of spinal CCL2（0.170 ± 0.009 vs. 0.047 ± 0.006；P < 0.001）were significantly increased on the first day after remifentanil infusion. Prior intrathecal injection of CCL2 neu⁃ tralizing antibody not only inhibited remifentanil-induced activation of microglia in the spinal cord（P < 0.001），but also mitigated remifentanil-induced thermal hyperalgesia and mechanical pain sensitivity（P < 0.05）.【Conclusion】CCL2 me⁃ diates the remifentanil-induced hyperalgesia by activating spinal microglia in rats.