大麻素CB_1受体活化对神经病理性疼痛大鼠脊髓背角嘌呤能P2X_2受体表达的抑制作用

目的:观察脊髓背角大麻素CB_1受体(CB_1R)在坐骨神经缩窄性损伤(CCI)所致的神经病理性疼痛中的作用及其对嘌呤能P2X_2受体表达的调节。方法:7~8周龄SD大鼠分为4组:(1)sham组;(2)CCI组;(3)CP55940+CCI组;(4)AM251+CP55940+CCI组。分别于CCI术前1 d,术后1、3、5、7、10、14 d测定热缩足反射潜伏期(TWL);免疫印迹技术检测各组大鼠损伤侧L_4~L_6段脊髓背角P2X_2受体表达。结果:CCI术后大鼠出现热痛敏,TWL明显缩短;鞘内给予非选择性大麻素受体激动剂CP55940可明显延长CCI大鼠TWL(P0.05);预先鞘内注射CB_1R拮抗剂AM251(0.05 mg/kg)可显著降低CP55940的镇痛效果(P0.05)。免疫印迹实验结果显示:CCI大鼠脊髓背角P2X_2受体在术后7、14 d表达明显增加(P0.05);鞘内给予CP55940可显著降低P2X_2受体表达(P0.05),而预先给予AM251可降低CP55940抑制P2X_2受体表达的效应(P0.05)。结论:脊髓背角CB_1受体激活对CCI所致的神经病理性疼痛具有良好的镇痛作用,其镇痛效应可能与抑制CCI大鼠嘌呤能P2X_2受体表达有关。

Inhibition of CB1 receptors activation on the expression of purinergic P2X2 receptors in spinal dorsal horn in neuropathic pain rats

Objective:To investigate the role of cannabinoid receptor 1 (CB1 R) activation in sciatic chronic constriction injury (CCI) induced neuropathic pain and its effect on the expression of P2X2 receptors (P2X2R).Methods:7-8 weeks of SD rats were divided into 4 groups:(1) sham group;(2) CCI group;(3) CP55940 + CCI group;(4) AM251 + CP55940 + CCI group.The values of thermal withdrawal latency (TWL) were measured at 1 day before operation,and at 1,3,5,7,10,14 after operation.The expression of P2X2R in spinal dorsal horn of injured ipsilateral L4 ～ L6 segment was detected by western blot.Results:TWL of CCI rats was significantly lower than sham group (P ＜0.05).Intrathecal injection of CP55940 (0.05 mg/kg),cannabinoid receptors agonist,prolonged the TWL of CCI rats (P ＜ 0.05).Pre-intrathecal injection of CB1 R antagonist AM251 (0.05 mg/kg) markedly blocked the analgetic effect of CP55940.The expression of P2X2 R in the ipsilateral (injured) L4,L5 and L6 spinal dorsal horn was markedly enhanced on days 7 d (P ＜ 0.05) and 14 d (P ＜ 0.05) after CCI.Intrathecal administration of CP55940 markedly inhibited the increased expression of P2X2 R after CCI.The inhibitory effect of CP55940 was blocked by AM251 (P ＜0.05).Conclusion:Activation of CB1R has analgesic effect to neuropathic pain induced by CCI.CB1R'S analgesic effect may be related to its inhibition of P2X2 receptors expression in spinal dorsal horn.