Tomić Maja A, Vucković Sonja M, Stepanović-Petrović Radica M, Ugresić Nenad D, Paranos Sonja Lj, Prostran Milica S, Bosković Bogdan
Department of Pharmacology, Faculty of Pharmacy, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Anesth Analg. 2007 Nov;105(5):1474-81, table of contents. doi: 10.1213/01.ane.0000287270.35176.3e.
We studied whether peripheral alpha2-adrenergic receptors are involved in the antihyperalgesic effects of oxcarbazepine by examining the effects of yohimbine (selective alpha2-adrenoceptor antagonist), BRL 44408 (selective alpha(2A)-adrenoceptor antagonist), MK-912 (selective alpha2C-adrenoceptor antagonist), and clonidine (alpha2-adrenoceptor agonist) on the antihyperalgesic effect of oxcarbazepine in the rat model of inflammatory pain.
Rats were intraplantarly (i.pl.) injected with the proinflammatory compound concanavalin A (Con A). A paw-pressure test was used to determine: 1) the development of hyperalgesia induced by Con A; 2) the effects of oxcarbazepine (i.pl.) on Con A-induced hyperalgesia; and 3) the effects of i.pl. yohimbine, BRL 44408, MK-912 and clonidine on the oxcarbazepine antihyperalgesia.
Both oxcarbazepine (1000-3000 nmol/paw; i.pl.) and clonidine (1.9-7.5 nmol/paw; i.pl.) produced a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by Con A. Yohimbine (260 and 520 nmol/paw; i.pl.), BRL 44408 (100 and 200 nmol/paw; i.pl.) and MK-912 (10 and 20 nmol/paw; i.pl.) significantly depressed the antihyperalgesic effects of oxcarbazepine (2000 nmol/paw; i.pl.) in a dose-dependent manner. The effects of antagonists were due to local effects since they were not observed after administration into the contralateral hindpaw. Oxcarbazepine and clonidine administered jointly in fixed-dose fractions of the ED(50) (1/4, 1/2, and 3/4) caused significant and dose-dependent reduction of hyperalgesia induced by Con A. Isobolographic analysis revealed an additive antihyperalgesic effect.
Our results indicate that the peripheral alpha2A and alpha2C adrenoceptors could be involved in the antihyperalgesic effects of oxcarbazepine in a rat model of inflammatory hyperalgesia.
我们通过检测育亨宾（选择性α2 - 肾上腺素能受体拮抗剂）、BRL 44408（选择性α(2A) - 肾上腺素能受体拮抗剂）、MK - 912（选择性α2C - 肾上腺素能受体拮抗剂）和可乐定（α2 - 肾上腺素能受体激动剂）对奥卡西平在大鼠炎性疼痛模型中抗痛觉过敏作用的影响，来研究外周α2 - 肾上腺素能受体是否参与奥卡西平的抗痛觉过敏作用。
大鼠足底注射促炎化合物伴刀豆球蛋白A（Con A）。采用 paw - pressure 试验来确定：1）Con A 诱导的痛觉过敏的发展；2）奥卡西平（足底注射）对 Con A 诱导的痛觉过敏的影响；3）足底注射育亨宾、BRL 44408、MK - 912 和可乐定对奥卡西平抗痛觉过敏作用的影响。
奥卡西平（1000 - 3000 nmol/爪；足底注射）和可乐定（1.9 - 7.5 nmol/爪；足底注射）均能显著且剂量依赖性地减轻 Con A 诱导的爪部炎性痛觉过敏。育亨宾（260 和 520 nmol/爪；足底注射）、BRL 44408（100 和 200 nmol/爪；足底注射）和 MK - 912（10 和 20 nmol/爪；足底注射）能以剂量依赖性方式显著抑制奥卡西平（2000 nmol/爪；足底注射）的抗痛觉过敏作用。拮抗剂的作用是局部性的，因为在对侧后爪给药后未观察到这些作用。奥卡西平和可乐定以 ED(50) 的固定剂量分数（1/4、1/2 和 3/4）联合给药，能显著且剂量依赖性地减轻 Con A 诱导的痛觉过敏。等效线图分析显示具有相加的抗痛觉过敏作用。
我们的结果表明，外周α2A 和α2C 肾上腺素能受体可能参与奥卡西平在大鼠炎性痛觉过敏模型中的抗痛觉过敏作用。
