The involvement of peripheral alpha(2)-adrenoceptors in the antihyperalgesic effect of oxcarbazepine in a rat model of inflammatory pain

We studied whether peripheral alpha(2)-adrenergic receptors are involved in the antihyperalgesic effects of oxcarbazepine by examining the effects of yohimbine (selective alpha(2)-adrenoceptor antagonist), BRL 44408 (selective alpha(2A)- adrenoceptor antagonist), MK-912 (selective alpha(2C)-adrenoceptor antagonist), and clonidine (alpha(2)-adrenoceptor agonist) on the antihyperalgesic effect of oxcarbazepine in the rat model of inflammatory pain. METHODS: 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. RESULTS: 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.), BRL44408 (100 and 200 nmol/paw,-i.pl.),and MK-912 (10and 20 nmol/paw;i.pl.) significantly depressed the antihyperalgesic effects of oxcarbazepine (2000 nmol/pav\T,I i.pl.) in a close-dependent mariner. The effects of antagonists were due to local effects since they were not observed after admirdstration into the contralateral hindpaw. Oxcarbazepine and clonidine administered jointly in fixed-dose fractions of the ED50 (1/4, 1/2, and 3/4) caused significant and dose-dependent reduction of hyperalgesia induced by Con A. lsobolographic analysis revealed an additive antihyperalgesic effect. CONCLUSIONS: Our results indicate that the peripheral a,A and a,c adrenoceptors could be involved in the antihyperalgesic effects of oxcarbazepine in a rat model of inflammatory hyperalgesia. (Anesth Analg 2007;105:1474-81