Bustamante D, Paeile C, Willer J C, Le Bars D
Department of Pharmacology, Faculty of Medicine, University of Chile, Santiago.
J Pharmacol Exp Ther. 1997 Jun;281(3):1381-91.
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 using a constant stimulus intensity (3 times threshold), and recruitment curves were built by varying the stimulus intensity from 0 to 7 times threshold. The intrathecal (i.t.) but not i.c.v. administration of aspirin, indomethacin, ketoprofen and lysine clonixinate resulted in dose-dependent depressions of the C-fiber reflex. In contrast, saline was ineffective. Regardless of the route of administration, the drugs never produced disturbances in heart rate and/or acid-base equilibrium. When a constant level of stimulation was used, 500 microg of aspirin i.t. induced a blockade of the reflex immediately after the injection, followed by a partial recovery. Indomethacin produced a stable depression, which reached 80 to 90% with an i.t. dose of 500 microg. Ketoprofen and lysine clonixinate produced a more stable effect; the highest doses (500 microg) produced a steady-state depression of approximately 50% for approximately 30 min. When the recruitment curves were built with a range of nociceptive stimulus intensities, all of the drugs except for indomethacin produced a dose-dependent decrease in the slopes and the areas under the recruitment curves without major modifications in the thresholds; indomethacin also induced a significant dose-related increase in the threshold. The orders of potency for both stimulation paradigms with the i.t. route were the same, namely aspirin > indomethacin > lysine clonixinate > or = ketoprofen. It is concluded that nonsteroidal anti-inflammatory drugs elicit significant antinociceptive effects at a spinal level, which do not depend on the existence of a hyperalgesic or inflammatory state. Such effects were not seen after injections within the lateral ventricle.
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。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倍阈值构建募集曲线。鞘内（i.t.）而非脑室内（i.c.v.）给予阿司匹林、吲哚美辛、酮洛芬和氯尼辛酯赖氨酸导致C纤维反射呈剂量依赖性抑制。相比之下，生理盐水无效。无论给药途径如何，这些药物从未引起心率和/或酸碱平衡紊乱。当使用恒定刺激水平时，500微克阿司匹林鞘内注射后立即引起反射阻断，随后部分恢复。吲哚美辛产生稳定的抑制作用，鞘内剂量为500微克时抑制率达到80%至90%。酮洛芬和氯尼辛酯赖氨酸产生更稳定的作用；最高剂量（500微克）在约30分钟内产生约50%的稳态抑制。当用一系列伤害性刺激强度构建募集曲线时，除吲哚美辛外，所有药物均使募集曲线的斜率和曲线下面积呈剂量依赖性降低，而阈值无重大改变；吲哚美辛还导致阈值显著剂量相关增加。鞘内给药途径的两种刺激模式的效力顺序相同，即阿司匹林>吲哚美辛>氯尼辛酯赖氨酸>或=酮洛芬。结论是，非甾体抗炎药在脊髓水平产生显著的抗伤害感受作用，这并不依赖于痛觉过敏或炎症状态的存在。侧脑室内注射后未观察到此类作用。
