COX抑制剂对神经病理性疼痛大鼠镇痛效果及机制

Analgesic effect of COX inhibitors and its mechanism in a rat model of neuropathic pain

目的观察COX抑制剂对慢性坐骨神经缩窄性损伤（CCI）神经病理性疼痛模型大鼠的镇痛效果及脊髓NR2B亚基表达,探讨其可能的机制。方法健康SD雄性大鼠体质量200~280 g,共36只,随机分为4组：CCI假手术组、CCI对照组、CCI吲哚美辛组、CCI帕瑞昔布组。各组大鼠于术前和用药前、用药后1、3、5、7 d测定机械性缩足反射阈。采用Westernblot方法测定脊髓NR2B亚基的蛋白表达。结果 CCI对照组、CCI吲哚美辛组和CCI帕瑞昔布组大鼠机械性缩足反射阈术后较术前明显降低（P〈0.05）,帕瑞昔布显著减轻CCI大鼠痛敏状态（P〈0.05）,吲哚美辛未显示镇痛效果;大鼠脊髓NR2B的表达,CCI吲哚美辛组和CCI帕瑞昔布组与CCI对照组比较无统计学差异（P〉0.05）。结论本研究观察到高选择性COX-2抑制剂帕瑞昔布治疗能够改善CCI模型神经病理性疼痛大鼠的机械性缩足反射阈,起到一定镇痛效果,但其机制与脊髓背角NR2B亚基系统可能无关。

Objective To investigate the effect of COX inhibitors on pain threshold and spinal N-methyl-D-aspartate（NMDA） receptor subunit 2B（NR2B） expression in a rat model of neuropathic pain.Methods Thirty-six male SD rats were randomly divided into sham-operated group,chronic constriction injury（CCI） of the sciatic nerve group,indomethacin＋CCI group,and parecoxib＋CCI group with corresponding treatments.All the rats were tested for mechanical withdrawal threshold,and at day 13 after the surgery,the rats were decapitated for detection of NR2B expression in the spinal cord at the L4-6 levels.Results The mechanical withdrawal threshold were lowered significantly after the operation in CCI,indomethacin＋CCI and parecoxib＋CCI groups（P0.05）.Parecoxib alleviated the hypersensitivity of CCI model rats but not affected spinal NR2B expressions（P0.05）.No significant differences were found in the mechanical withdrawal threshold or spinal NR2B expression between CCI group and indomethacin＋CCI group（P0.05）.Conclusion Parecoxib can alleviate neuropathic hypersensitivity in rats,but this effect may not be associated with NR2B expression in the spinal cord.