Dirig D M, Yaksh T L
Department of Pharmacology, University of California, San Diego, La Jolla, USA.
J Pharmacol Exp Ther. 1995 Oct;275(1):219-27.
Both gamma-aminobutyric acid (GABA)A and GABAB receptor subtypes have been implicated in spinally mediated antinociception in acute pain models. In the current study, the formalin test was used as a model of protracted nociception to examine the effect of intrathecally (i.t.) administered baclofen (GABAB agonist), muscimol (GABAA agonist) or midazolam (a benzodiazepine) on antinociception. At doses that did not affect motor function, baclofen (0.3 and 1.0 micrograms, i.t.) decreased the flinch response in a dose-dependent manner during Phase 1 and Phase 2. This effect was reversible by the GABAB-specific antagonist, CGP35348 ([P-(3-aminopropyl)-P-diethoxymethyl-phosphinic acid]). Muscimol (0.3 and 1.0 microgram i.t.) evoked a dose-dependent, bicuculline-reversible decrease in flinching during Phase 1 and Phase 2, but midazolam had no effect on either phase. No attenuation of the quiescent period between Phase 1 and Phase 2 was seen upon administration of baclofen, muscimol or midazolam. Additionally, no increase in nocifensive behavior was observed upon administration of either GABAA or GABAB antagonists alone. Therefore, our conclusions are that both GABAA and GABAB agonists are antinociceptive at the spinal cord level and that endogenous spinal GABA levels are insufficient for a GABA potentiator to act alone in an antinociceptive manner.
在急性疼痛模型中，γ-氨基丁酸（GABA）A和GABAB受体亚型均与脊髓介导的抗伤害感受有关。在本研究中，福尔马林试验被用作持续性伤害感受的模型，以检查鞘内注射巴氯芬（GABAB激动剂）、蝇蕈醇（GABAA激动剂）或咪达唑仑（一种苯二氮䓬类药物）对抗伤害感受的影响。在不影响运动功能的剂量下，巴氯芬（0.3和1.0微克，鞘内注射）在第1阶段和第2阶段以剂量依赖性方式降低了退缩反应。这种作用可被GABAB特异性拮抗剂CGP35348（[P-（3-氨丙基）-P-二乙氧基甲基次膦酸]）逆转。蝇蕈醇（0.3和1.0微克，鞘内注射）在第1阶段和第2阶段引起剂量依赖性、荷包牡丹碱可逆的退缩减少，但咪达唑仑对两个阶段均无影响。给予巴氯芬、蝇蕈醇或咪达唑仑后，未观察到第1阶段和第2阶段之间静止期的缩短。此外，单独给予GABAA或GABAB拮抗剂后，未观察到伤害性反应行为增加。因此，我们的结论是，GABAA和GABAB激动剂在脊髓水平均具有抗伤害感受作用，并且内源性脊髓GABA水平不足以使GABA增强剂单独以抗伤害感受方式起作用。
