坐骨神经切断大鼠脑脊液中CCK-8含量的动态变化及其与吗啡镇痛的关系  

RELATIONS BETWEEN THE EFFECT OF MORPHINE INDUCD ANALGESIA AND THE CONTENT OF CCK-8 IN CEREBRO SPINAL FLUID AFTER SCIATIC NERVE TRANSECTION IN RATS

作　　者：刘苏星[1] 沈上[1] 于英心[1] 韩济生[1] 罗非[1] 

机构地区：[1]北京大学神经科学研究所

出　　处：《中国疼痛医学杂志》2004年第6期352-356,共5页Chinese Journal of Pain Medicine

基　　金：国家自然科学基金(30170307;30370461);211工程二期项目;北京大学985青年启动项目资助

摘　　要：目的研究神经源性疼痛时吗啡镇痛效应的降低与中枢八肽胆囊收缩素(CCK8)的释放量之间的关系。方法以切断大鼠单侧坐骨神经作为引起神经痛的动物模型,用放射免疫分析法,观察术后第3,7,10和14天脑脊液中CCK8ir含量的变化,并在相应的时间点分别皮下注射吗啡(4mg/kg)和CCKB受体拮抗剂L365,260(0.5mg/kg),观察痛阈(辐射热甩尾潜伏期)的变化。结果(1)大鼠单侧坐骨神经切断后一周,脑脊液中CCK8样免疫活性物质(CCK8ir)的浓度(代表中枢CCK8的释放量)增加了125%,此时吗啡的镇痛效果降低,而CCK拮抗剂使吗啡镇痛效果提高。(2)坐骨神经切断后1.5～2周,中枢CCK8释放减少或保持正常水平,此时吗啡镇痛效果正常,CCK拮抗剂也不能使其效应进一步提高。(3)假手术组大鼠于第14天(第四次注射吗啡)时,吗啡作用减弱(发生耐受),此时CCK拮抗剂显示出对吗啡镇痛的加强作用。结论单侧坐骨神经切断后一周吗啡镇痛效果减弱,可能与当时中枢CCK8释放过多有关。切断坐骨神经后中枢释放CCK8水平的变化,是影响阿片镇痛的重要因素。Objective: To investigate the relations between the release of cholecystokinin octopeptide (CCK 8) in spinal cord and the decrease of morphine induced analgesia under neuropathic pain condition. Methods: Sciatic nerve transection in rats was used as an animal model of neuropathic pain. The contents of CCK 8 immunoreactivity ( ir) in cerebral spinal fluid (CSF) were determined 3, 7, 10, and 14 days after surgery. Pain thresholds (tail flick latency) were also monitored simultaneously after s.c. injection of morphine (4 mg/kg) and a CCK B receptor antagonist, L 365,260 (0.5 mg/kg). Results: (1) One week after unilateral sciatic nerve transection, CSF concentration of CCK 8 ir showed a 125% increase. The effect of morphine induced analgesia was significantly decreased, which could be reversed by CCK B antagonist. (2) In 1.5 2 weeks after surgery, the level of spinal CCK 8 also either reduced or kept normal. No change to morphine analgesia could be observed, and CCK B antagonist had no further effect. (3) Rats with sham surgery showed decreased morphine analgesia (i.e., tolerance) on the 14 th day after the 4 th injection of morphine. The analgesic effect of morphine could be enhanced by CCK B receptor blocker. Conclusion: The diminished analgesic effect of morphine maybe due to an over release of CCK 8. The level of centrally released CCK 8 may play an important role in the variation of opioid analgesia after sciatic nerve transection.

关 键 词：坐骨神经切断 吗啡 八肽胆囊收缩素 L-365 260 

分 类 号：R96[医药卫生—药理学]