Intrathecal injection of oxycodone hydrochloride reduces neuropathic pain in rat model of chronic constriction injury via inhibition of microglial c-JNK/CXCL1 signal / 中国医师杂志

ABSTRACT

Objective To observe the effect of intrathecal injection (IT) of oxycodone hydrochloride on neuropathic pain and spinal cord level of microglial c-Jun N-terminal kinase/chemokine (C-X-C motif) ligand 1 (c-JNK/CXCL) 1signal in rat model of chronic constriction injury (CCI).Methods Male Sprague-Dawley rats were randomly divided into five groups (n =40 per group)sham group (intrathecal normal saline,IT NS),CCI group (CCI + IT NS),oxy group (CCI + IT 5 μg/30 μl oxy),mino group (CCI + IT 5 μg/30 μl Minocycline),and c-JNK inhibitor group (SP group,CCI + IT 5 μg/30 μl SP600125).The lumbar intrathecal catheters were implanted in L5-6 of rats and CCI models were established as previously described.The thermal and mechanical nociceptive thresholds were assessed by paw withdrawal latency (PWL) to radiant heat and von Frey filaments.The oxycodone,minocycline and SP600125 were administered intrathecally for 3 days before surgery.The spinal cord expression of Ⅰ ba-1,p-c-JNK and CXCL1 proteins assessed by Western blot.Immunofluorescence staining was performed to examine microglia morphology and the number of Ⅰ ba-1 positives cells in dorsal horn of injured spinal cord at 7 days post-IR.Results Compared to sham group,rats in CCI group had significantly lower mechanical and thermal pain thresholds,but higher spinal proteins expression of Ⅰ ba-1,and p-c-JNK and CXCL1 (P ＜0.05).Rats in oxy group,mino group and SP group had significantly higher mechanical and thermal pain thresholds and significantly lower proteins expression of Ⅰ ba-1,p-c-JNK and CXCL1 compared to those in CCI group (at any observed time-point after ligation,but most significantly at 7days,P ＜ 0.05).At the 7days after surgery,microglial cells in CCI group transformed from the ramified shape to amoeboid macrophage-like shape by immunofluorescence staining with the increases of Ⅰ ba-1 positive cells;while the other three groups exhibited hypertrophic morphology with less number Ⅰ ba-1 positive cells (P ＜ 0.05).There were no significant differences between these three groups at any observed time (P ＞ 0.05).Conclusions Intrathecal injection of oxycodone hydrochloride can relieve CCI-induced neuropathic pain by down-regulation microglial c-JNK/CXCL1 signal in spinal cords.Provide new therapeutic targets for clinical treatment of neuropathic pain.