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脊髓大麻素受体-1拮抗剂抑制炎性痛大鼠的吗啡耐受效应
Cannabinoid Receptor-1 Antagonist Inhibits the Process of Morphine Tolerance in Rats with Inflammatory Pain

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DOI:
作者:
郭茜
GUO QIAN
作者单位:
上海交通大学医学院附属瑞金医院
Department of Anesthesiology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University
关键词:
大麻素受体-1；吗啡耐受；炎性痛；脊髓背角
CB1; morphine tolerance; inflammatory pain; spinal dorsal horn
摘要:
目的 观察吗啡对炎性痛治疗时产生耐受效应的模型大鼠脊髓背角大麻素受体-1（cannabinoid receptor-1，CB1）蛋白表达变化，考察CB1受体拮抗剂对炎性痛大鼠吗啡耐受效应的干预作用。方法 成年雄性SD大鼠40只行鞘内置管术后，随机分为4组（n=10）。对照组（Sham组）于右足足底注射生理盐水100μl 3天后鞘内注射生理盐水10μl；CFA组右足足底注射弗氏完全佐剂100μl 3天后鞘内给予生理盐水10μl；吗啡组（Mor组）右足足底注射弗氏完全佐剂100μl 3后鞘内给予吗啡10μg/10μl；AM251组足底注射弗氏完全佐剂100μl 3天后鞘内给予吗啡10μg + AM251 5 nmol/10μl。连续给药7d，每日1次。采用热缩脚潜伏期（PWL）评价痛行为学，于鞘内给药后第8天处死大鼠，取脊髓L2-4节段组织，采用Western blot法测定CB1蛋白表达。结果 Mor组大鼠在鞘内给予吗啡第7天即形成了稳定的吗啡耐受，表现为PWL值明显低于Sham组（t=14.69, P<0.001），而与CFA组无明显差异（t=1.732，P>0.05）。Mor组大鼠吗啡耐受形成后脊髓背角CB1蛋白表达明显高于Sham组（t=5.018, P<0.001）和CFA组（t=3.331, P<0.05）。而AM251组大鼠给药后1、3、5、7天PWL无统计学差异（F=0.886，P=0.459）。结论 CB1拮抗剂AM251可抑制吗啡耐受形成。
Objective To observe changes of CB1 protein expression in spinal dorsal horn of morphine tolerant rats with inflammatory pain, so as to explore the effect of CB1 antagonist in the process of morphine tolerance in rats. Methods Forty male adult Sprague-Dawley rats implanted intrathecal catheters were randomly divided into four groups(n=10). The control group (Sham group) were injected 100μl saline intraplantar then 10μl saline intrathecal 3 days later.CFA group was given 100μl CFA intraplantar and 10μl saline intrathecal. Mor group was given 100μl CFA intraplantar and 10μg morphine intrathecal. AM251 group was given 100μl CFA intraplantar and 10μg morphine plus AM251 5 nmol, once daily for 7 days. Thermal paw withdrawal latency (PWL) of rats was examined to evaluate their heat hyperalgesia. Rats were killed at 8th day after intrathecal administration of drugs and the expression of CB1 in spinal lumber 2-4 tissues was detected by Western blot method. Results Morphine tolerance formed stably in Mor group on day 7. There was no significant difference between Mor group and CFA group on the 7th day（t=1.732，P>0.05）. The expression of CB1 in Mor group was obviously higher than that in Sham group（t=5.018, P<0.001） and CFA group（t=3.331, P<0.05） after morphine tolerance formed. The PWL of AM251 group had no significant change after intrathecal administration（F=0.886，P=0.459）. Conclusions CB1 antagonist can inhibit the development of morphine tolerance.

 

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