目的观察鞘内注射大麻素CB2受体激动剂AM1241对慢性坐骨神经结扎(CCI)大鼠热痛阈和Iba1表达的影响,探讨CB2受体在大鼠神经病理性疼痛中的作用。方法成年SD大鼠24只,随机分:sham组(假手术组)、CCI组(坐骨神经结扎+鞘内注射生理盐水)、AM1241处理组(慢性坐骨神经结扎+鞘内注射AM124110。M);连续14d鞘内注射,在术后第1,3,5,7,10,14天测定给药0.5h后热缩足潜伏期(TwL)。在第7,14天免疫组化观察背角IbM表达变化。结果大鼠CCI术后1d即可形成稳定的热痛敏;与sham组相比,CCI组第7,14天背角IbM表达明显上调(P〈0.05);与CCI组相比,鞘内注射CB2受体激动剂AM1241(10^-3M)明显延长CCI大鼠TwL(P〈0.01),但鞘内注射AM1241对CCI大鼠第7,14天背角Iba1表达上调没有明显影响。结论鞘内注射大麻素CB2受体激动剂AM1241可以发挥良好的镇痛效应,但AM1241不影响CCI大鼠脊髓背角IbM表达的上调。
Objective To investigate the effects of intrathecal injection of AM1241, the CB2 receptor selective agonist, on rat thermal withdrawal latency (TWL) and Ibal expression in dorsal horn with chronic constriction injury (CCI) of the sciatic nerve and further explore the role of CB2 receptor in neuropathic pain. Methods SD rats were randomly divided into three groups ( n = 8 ) : sham group (sham operation), CCI group (CCI + intrathecal injection of saline) and AM1241 group (CCI + in- trathecal injection of 10-3M AM1241 ). The intrathecal injection was administrated for continuous 14 d. Heat hyperalgesia were evaluated by TWL detection 1, 3, 5, 7, 10 and 14 d after surgery, respective- ly. The Ibal expression in dorsal horn was assessed by immunohistochemistry 7 and 14 d after surgery. Results TWL in CCI group were significantly lower than that in sham group 1,3, 5,7, 10 and 14 d af- ter surgery (P 〈 0. 05 ). Compared with the CCI group, intrathecal injection of AM1241 significantly prolonged rat TWL (P 〈0.01 ). Compared with the sham group, the Ibal expression in dorsal horn was significantly increased 7 and 14 d after surgery (P 〈 0.05 ). However, the intrathecal injection of AM1241 had no significant effects on CCI - induced increase of Ibal expression 7 and 14 d after surger- y. Conclusion Intrathecal injection of AM1241 could produce an obvious anti - allodynia activities in rat sciatic nerve CCI model but have no significant effects on Ibal expression in dorsal horn of CCI rats.