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

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(CCK-8)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CCK-8-ir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L-365，260(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CCK-8样免疫活性物质(CCK-8-ir)的浓度(代表中枢CCK-8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CCK-8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CCK-8释放过多有关。切断坐骨神经后中枢释放CCK-8水平的变化，是影响阿片镇痛的重要因素。

Abstract:

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.