Guirimand F, Chauvin M, Willer J C, Le Bars D
INSERM U161, Paris, France.
J Pharmacol Exp Ther. 1995 May;273(2):830-41.
A C-fiber reflex elicited by electrical stimulation within the territory of the sural nerve was recorded from the ipsilateral biceps femoris muscle in anesthetized rats. The temporal evolution of the response was studied by using a constant stimulus intensity (3 x threshold) and recruitment curves were built by varying the stimulus intensity from 0 to 7 x threshold. Low (0.5-1 mg/kg) and high doses (4-10 mg/kg) of i.v. morphine induced a facilitation and a depression of the C-fiber reflex, respectively, in a dose-dependent manner. The ED50 (95% confidence limit) for the depressive effect with a stimulus intensity of 3 x control threshold was 3.8 (3.1-4.8) mg/kg. Increasing the stimulus intensity was associated with a shift of the dose-response curve to the right, without a change of slope. In the 1.5 to 7 x threshold range, ED50 were linearly related to the stimulus intensity. Intravenous naloxone (0.4 mg/kg) completely antagonized the facilitation or depression induced by morphine. Low doses (1-10 micrograms/kg; i.v.) of buprenorphine facilitated the reflex in a fashion similar to morphine. Higher doses (30-1000 micrograms/kg; i.v.) elicited a biphasic effect on the C-fiber reflex: depressive and facilitatory with weak and strong stimulus intensities, respectively. These results are discussed in terms of there being an intrinsic efficacy for the depressive effects of morphine and buprenorphine and of their clinical potencies. Various hypotheses are suggested regarding the facilitations of the C-fiber reflex.
在麻醉大鼠中,从同侧股二头肌记录腓肠神经支配区域内电刺激诱发的C纤维反射。通过使用恒定刺激强度(3倍阈值)研究反应的时间演变,并通过将刺激强度从0变化到7倍阈值来构建募集曲线。静脉注射低剂量(0.5 - 1毫克/千克)和高剂量(4 - 10毫克/千克)吗啡分别以剂量依赖性方式促进和抑制C纤维反射。在刺激强度为3倍对照阈值时,抑制作用的半数有效剂量(ED50,95%置信区间)为3.8(3.1 - 4.8)毫克/千克。增加刺激强度会使剂量 - 反应曲线向右移动,但斜率不变。在1.5至7倍阈值范围内,ED50与刺激强度呈线性相关。静脉注射纳洛酮(0.4毫克/千克)完全拮抗吗啡诱导的促进或抑制作用。低剂量(1 - 10微克/千克;静脉注射)丁丙诺啡以类似于吗啡的方式促进反射。高剂量(30 - 1000微克/千克;静脉注射)对C纤维反射产生双相作用:分别在弱和强刺激强度下产生抑制和促进作用。根据吗啡和丁丙诺啡的抑制作用的内在效力及其临床效能对这些结果进行了讨论。针对C纤维反射的促进作用提出了各种假设。