Goodchild C S, Guo Z, Musgreave A, Gent J P
Department of Anaesthesia, University of Leeds, Australia.
Br J Anaesth. 1996 Dec;77(6):758-63. doi: 10.1093/bja/77.6.758.
Intrathecal midazolam causes antinociception by combining with spinal cord benzodiazepine receptors. This effect is reversible with doses of naloxone, suggesting involvement of spinal kappa or delta but not mu opioid receptors. The antinociceptive effects of intrathecally administered drugs in the spinal cord were demonstrated by measurements of the electrical current threshold for avoidance behaviour in rats with chronically implanted lumbar intrathecal catheters. A comparison was made of suppression by two opioid selective antagonists (nor-binaltorphimine (kappa selective) and naltrindole (delta selective)) of spinal antinociception caused by equipotent doses of opioids selective for different receptor subtypes (U-50488H (kappa), DSLET and DSBULET (delta), fentanyl (mu)) and the benzodiazepine midazolam. Nor-binaltorphimine selectively suppressed the effects of U-50488H but not midazolam or fentanyl. However, the delta selective antagonist, naltrindole, caused dose-related suppression of antinociception produced by both delta opioid agonists and midazolam with the same ED50 (0.5 nmol). We conclude that intrathecal midazolam caused spinally mediated antinociception in rats by a mechanism involving delta opioid receptor activation.
鞘内注射咪达唑仑通过与脊髓苯二氮䓬受体结合产生抗伤害感受作用。这种作用可被纳洛酮剂量逆转，提示脊髓κ或δ阿片受体参与其中，而非μ阿片受体。通过测量慢性植入腰段鞘内导管大鼠回避行为的电流阈值，证实了鞘内给药药物在脊髓中的抗伤害感受作用。比较了两种阿片类选择性拮抗剂（诺宾那托啡（κ选择性）和纳曲吲哚（δ选择性））对不同受体亚型选择性阿片类药物（U - 50488H（κ）、DSLET和DSBULET（δ）、芬太尼（μ））和苯二氮䓬类药物咪达唑仑等效剂量引起的脊髓抗伤害感受的抑制作用。诺宾那托啡选择性抑制U - 50488H的作用，但不抑制咪达唑仑或芬太尼的作用。然而，δ选择性拮抗剂纳曲吲哚对δ阿片类激动剂和咪达唑仑产生的抗伤害感受均产生剂量相关的抑制作用，且二者的半数有效剂量（ED50）相同（0.5 nmol）。我们得出结论，鞘内注射咪达唑仑通过涉及δ阿片受体激活的机制在大鼠中引起脊髓介导的抗伤害感受。
