中文摘要：

目的观察脊髓背角大麻素受体2（CB_2R）是否参与大麻素类药物CP55940对慢性坐骨神经缩窄性损伤（CCI）所致神经病理性疼痛的镇痛作用,并初步探讨其机制。方法成年SD大鼠随机分为4组：对照组、CCI组（鞘内注射DMSO生理盐水）、CP55940＋CCI组（鞘内注射0.05 mg/kg CP55940）、AM630＋CP55940＋CCI组（鞘内注射10~（-8）mol/L AM630,20 min后再给予0.05 mg/kg CP55940）。各组大鼠均于鞘内置管5 d后行CCI术,术后连续14 d鞘内注射给药,每天1次;于CCI术前1 d,术后第1、3、5、7、10、14天鞘内给药1 h后测定热缩足潜伏期（TWL）。分别于CCI术后第7天和第14天处死大鼠,取术侧L_4~L_6脊髓背角,采用免疫印迹技术检测脊髓背角CB_2R及丝裂原活化蛋白激酶家族中p38（p38 MAPK）表达情况。结果大鼠CCI术后即形成稳定的热痛敏,TWL明显缩短;鞘内给予非选择性CB受体激动剂CP55940（0.05mg/kg）可明显延长CCI大鼠TWL（P〈0.05）;选择性CB_2受体拮抗剂AM630（10~（-8）mol/L）可部分阻断CP55940的镇痛效果（P〈0.05）。免疫印迹实验结果显示,CCI术可导致术侧脊髓背角CB_2R、p38表达增加（P〈0.01）;鞘内给予CP55940可诱导CCI所致的CB_2R表达进一步增加（P〈0.01）,但明显降低CCI所致的p38表达增加（P〈0.01）;预先鞘内注射CB_2R拮抗剂AM630可阻断CP55940对CB_2R及p38表达的影响（P〈0.01）。结论鞘内给予大麻素类药物CP55940对CCI所致的神经痛具有良好的镇痛效应,CB_2R通过可能抑制脊髓背角胶质细胞p38的活性参与了CP55940的镇痛作用。

英文摘要：

Objective The aim of this study is to examine whether CB_2 receptor is involved in analgesia of cannabinoids on neuropathic rats with chronic constriction injury（ CCI） of the sciatic nerve. Methods Healthy adult SD rats were randomly divided into control group,CCI group（ intrathecal DMSO saline）,CP55940 ＋ CCI group（ CP55940 0. 05 mg /kg） and AM630 ＋ CP55940 ＋ CCI group（ AM630 10~（-8）mol / l; CP55940 0. 05 mg / kg）.SD rats in all groups were intrathecally cathetered at 5 d before CCI operation. All rats were tested for heat hyperalgesia of the plantar surface of the hindpaw 1 day before surgery and 1,3,5,7,10 and 14 d after surgery.AM630,CP55940 and DMSO saline were intrathecally administered once a day for 14 consecutive days after CCI operation. The values of thermal withdrawal latency（ TWL） were examined at 1h after intrathecal injection. The expression of CB_2 receptors and p38 mitogen-activated protein kinase（ MAPK） were detected by western blot assay. Results TWL in CCI group were significantly lower than those in sham group on post-operative day（ P〈0. 05）. Intrathecal administration of CP55940（ cannabinoid receptor agonist,0. 05 mg / kg） markedly suppressed the decrease in TWL after nerve injury（ P〈0. 05）. Intrathecal administration of AM630（ CB_2 receptor antagonist,10~（-8）mol / l） markedly suppressed the analgesic effect of CP55940. The immunoblotting assay showed that the expression of CB_2 receptor and p38 were markedly enhanced in the ipsilateral dorsal horn on days 7（ P〈0. 01） and 14（ P〈0. 01） after nerve injury. Intrathecal administration of CP55940 further enhanced the expression of CB_2 receptor after CCI（ P〈0. 01）,but markedly suppressed the increased expression of p38 after CCI（ P〈0. 01）. Intrathecal administration of AM630 blocked the effect of CP55940 on expression of CB_2receptors（ P〈0. 01） and p38（ P〈0. 01）. Conclusion These data indicate that intrathecal administration of cannabinoid receptor agonis