中文摘要：

目的观察脊髓背角大麻素受体1（cannabinoid receptor 1,CB1R）在大麻素类药物CP55940对慢性坐骨神经结扎（chronic constriction injury,CCI）所致的神经病理性疼痛大鼠镇痛效应中的作用,并初步探讨其机制。方法 8周龄雄性SD大鼠56只分为7组：1假手术组,2CCI组（鞘内注射DMSO生理盐水）,3AM251＋CCI组（鞘内注射10^-8mol/L AM251）,4～6CP55940（0.01、0.05、0.20 mg/kg）＋CCI组（鞘内注射0.01、0.05、0.20 mg/kg CP55940）,7AM251＋CP55940＋CCI组（预先鞘内注射10^-8mol/L AM251,10 min后给予0.05 mg/kg CP55940）;每组8只。假手术组大鼠不进行鞘内置管,仅游离坐骨神经不结扎;其余各组大鼠在鞘内置管5 d后行CCI术,术后分别鞘内给予各种药物。分别在CCI术前1 d,术后1、3、5、7、10、14 d鞘内给药1 h后测定热缩足潜伏期（thermal withdrawal latency,TWL）;术后第7、14 d处死大鼠,取术侧L4～L6脊髓背角,采用免疫印迹技术检测脊髓背角CB1R及蛋白激酶A（protein kinase A,PKA）表达的变化。结果大鼠CCI术后即形成稳定的热痛敏,TWL明显缩短;与CCI组相比,鞘内给予非选择性CB受体激动剂CP55940 0.05 mg/kg可明显延长CCI大鼠TWL（P〈0.05）;选择性CB1R拮抗剂AM251（10^-8mol/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,与假手术组相比,CCI组大鼠在术后7、14 d术侧脊髓背角CB1R、PKA表达明显增加（P〈0.05）;鞘内给予CP55940可显著降低CCI大鼠的PKA表达（P〈0.05）;CB1R拮抗剂AM251显著降低了CCI大鼠的CB1R表达（P〈0.05）,同时阻断了CP55940降低CCI大鼠PKA表达的效应（P〈0.05）。结论鞘内注射大麻素类药物CP55940对CCI所致的神经痛具有良好的镇痛效应,CB1受体可能通过抑制PKA的活性参与了CP55940的镇痛作用。

英文摘要：

Objective To determine the role of cannabinoid receptor 1（ CB1R） in the analgesic effects of CP55940,a synthetic cannabinoid,in neuropathic rats with chronic constriction injury（ CCI） of the sciatic nerve.Methods Fifty-six healthy male SD rats（ 8 weeks old） were divided into 7 groups：（ 1） sham group（ n = 8）,（ 2） CCI group（ intrathecal injection of DMSO saline,n = 8）,（ 3） AM251 ＋ CCI group（ intrathecal injection of 10^-8mol /L AM251,n = 8）,（ 4） to（ 6） CP55940 ＋ CCI group（ intrathecal injection of 0.01,0.05,and 0.20 mg /kg CP55940,respectively,n = 8） and（ 7） AM251 ＋ CP55940 ＋ CCI group（ intrathecal injection of 10^-8mol /L AM251,followed by 0.05 mg /kg CP55940 in 10 min later,n = 8）.In the sham-operated rats,the sciatic nerve was visualized and left intact.SD rats in other 6 groups were intrathecally cathetered at 5 d before CCI operation.All rats were tested for heat hyperalgesia of the plantar surface of the hind paw in 1 d before surgery and 1,3,5,7,10 and 14 d after surgery.AM251,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 1 h after intrathecal injection.The expression of CB1 R and protein kinase A（ PKA） was detected by Western blotting.Results TWL in the CCI group was significantly lower than that in the sham group after operation（ P〈0.05）.Intrathecal administration of CP55940（ 0.01,0.05 and 0.20 mg /kg） markedly suppressed the decrease of TWL in a dose-dependent manner after nerve injury（ P〈0.05）.Intrathecal administration of AM251（ CB1 R antagonist,10^-8mol /L） markedly suppressed the analgesic effect of CP55940（ 0.05 mg /kg）.Western blot assay showed that the expression of CB1 R and PKA was markedly enhanced in the ipsilateral dorsal horn on days 7（ P〈0.05） and 14（ P〈0.05） after nerve injury.Intrathecal administration of CP55940 markedly suppressed the increased expressi