Effects of spinal cholecystokinin receptor antagonists on morphine antinociception in a model of visceral pain in the rat.
Effects of spinal cholecystokinin receptor antagonists on morphine antinociception in a model of visceral pain in the rat.
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发表时间：
2000-02
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通讯作者：
A. E. Friedrich;G. Gebhart
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作者：
A. E. Friedrich;G. Gebhart
本研究的目的是确定脊髓胆囊收缩素（CCK）受体拮抗剂对吗啡镇痛作用的内脏伤害感受模型，结直肠扩张，慢性结肠炎大鼠和溶剂处理的对照。结肠内滴注2，4，6-三硝基苯磺酸（TNBS）后3 - 5天，对所有结肠直肠扩张压力（10-80 mm Hg）的内脏反应明显增强。溶剂处理大鼠鞘内注射吗啡（0.93微克）的艾德（50）在TNBS处理大鼠中产生显著更大的抗伤害感受。鞘内注射丙谷胺，一种非选择性CCK受体拮抗剂，剂量依赖性地增强吗啡的镇痛作用，在车辆处理的大鼠，但不是在TNBS处理的大鼠。同样，L-365，260，一种特异性CCK（B）受体拮抗剂，剂量依赖性地增加吗啡的镇痛作用，在溶剂处理的大鼠，但在大鼠与TNBS诱导的结肠炎症没有效果。L-364，718是一种特异性CCK（A）受体拮抗剂，对吗啡镇痛作用无影响。这些数据表明，CCK，在CCK（B）受体的作用，参与调节吗啡抗伤害性内脏刺激后。然而，CCK受体拮抗剂不再增强吗啡镇痛后，注入结肠TNBS，内脏炎症可能导致脊髓CCK释放减少。
The objective of the present study was to determine the effects of spinal cholecystokinin (CCK) receptor antagonists on morphine antinociception in a model of visceral nociception, colorectal distension, in rats with chronic colonic inflammation and vehicle-treated controls. Three to five days after intracolonic instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS), an enhanced visceromotor response to all pressures of colorectal distension (10-80 mm Hg) was evident. The ED(50) of intrathecal morphine (0.93 microgram) in vehicle-treated rats produced significantly greater antinociception in TNBS-treated rats. Intrathecal proglumide, a nonselective CCK receptor antagonist, dose dependently enhanced the antinociceptive effect of morphine in vehicle-treated rats, but not in TNBS-treated rats. Similarly, L-365, 260, a specific CCK(B) receptor antagonist, dose dependently increased morphine's antinociceptive effects in vehicle-treated rats but had no effect in rats with TNBS-induced colonic inflammation. L-364,718, a specific CCK(A) receptor antagonist, had no effect on morphine antinociception in either vehicle-treated or TNBS-treated rats. These data indicate that CCK, acting at the CCK(B) receptor, is involved in modulating morphine antinociception following a noxious visceral stimulus. However, CCK receptor antagonists no longer enhance morphine antinociception after instillation of intracolonic TNBS, suggesting that visceral inflammation may lead to a reduction in spinal CCK release.