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

Inhibition of CB_1 receptors activation on the expression of purinergic P2X_2 receptors in spinal dorsal horn in neuropathic pain rats

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(P<0.05);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(P<0.05)。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(P<0.05);鞘内给予CP55940可显著降低P2X_2受体表达(P<0.05),而预先给予AM251可降低CP55940抑制P2X_2受体表达的效应(P<0.05)。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。

Objective： To investigate the role of cannabinoid receptor 1 （CBIR） 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 CB1R antagonist AM251 （0.05 mg/kg） markedly blocked the an- algetic effect of CP55940. The expression of P2X2R in the ipsilateral （injured） L4, L5 and L5 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 P2X2R 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 CCLCB1 R＇s analgesic effect may be related to its inhibition of P2X2 receptors expression in spinal dorsal horn.