Luger T J, Hayashi T, Weiss C G, Hill H F
Department of Anesthesiology, University of Washington, School of Medicine, Seattle 98195, USA.
Eur J Pharmacol. 1995 Mar 6;275(2):153-62. doi: 10.1016/0014-2999(94)00759-z.
The authors investigated the effects of spinal and supraspinal administration of the benzodiazepine receptor agonist midazolam alone and with opioids on tests of nociception (tail-flick and hot-plate tests) and motor function (catalepsy) in rats. At the spinal level, the dose-response curves for peak effect and area under the curve for morphine were shifted to the left (indicating potentiation) by a submaximal dose of intrathecal (i.t.) midazolam (20 micrograms) in both nociceptive tests. Additionally, 2.5 micrograms of i.t. midazolam, a dose having no effect when given alone, increased antinociception in both tests when given with i.t. morphine. Isobolographic analysis confirmed that i.t. injection of midazolam potentiated antinociception induced by i.t. morphine. At the supraspinal level, intracerebroventricular (i.c.v.) injection of 4 micrograms of midazolam inhibited morphine antinociception, i.e., the dose-response curve for morphine in the hot-plate test shifted to the right. Midazolam did not affect morphine antinociception in the tail-flick test. Catalepsy occurred only when the highest doses of i.t. or i.c.v. morphine or midazolam were injected alone. The differing effect of midazolam on morphine-induced antinociception suggests that different mechanisms are involved in the spinal cord and brain.
作者研究了单独给予苯二氮䓬受体激动剂咪达唑仑以及将其与阿片类药物联合经脊髓和脊髓上途径给药对大鼠痛觉测试（甩尾和热板试验）和运动功能（僵住症）的影响。在脊髓水平，在两项痛觉测试中，鞘内注射（i.t.）亚最大剂量的咪达唑仑（20微克）使吗啡的峰值效应剂量 - 反应曲线和曲线下面积向左移动（表明增强作用）。此外，2.5微克鞘内注射的咪达唑仑单独给药时无作用，但与鞘内注射吗啡合用时，在两项测试中均增强了镇痛作用。等效线图分析证实，鞘内注射咪达唑仑增强了鞘内注射吗啡诱导的镇痛作用。在脊髓上水平，脑室内（i.c.v.）注射4微克咪达唑仑抑制了吗啡的镇痛作用，即热板试验中吗啡的剂量 - 反应曲线向右移动。咪达唑仑在甩尾试验中不影响吗啡的镇痛作用。仅在单独注射最高剂量的鞘内或脑室内吗啡或咪达唑仑时才会出现僵住症。咪达唑仑对吗啡诱导的镇痛作用的不同影响表明，脊髓和脑涉及不同的机制。
