Vučković, Sonja M. (7003869333)Sonja M. (7003869333)VučkovićTomić, Maja A. (7006939166)Maja A. (7006939166)TomićStepanović-Petrović, Radica M. (6506683297)Radica M. (6506683297)Stepanović-PetrovićUgrešić, Nenad (6602152735)Nenad (6602152735)UgrešićProstran, Milica Š. (7004009031)Milica Š. (7004009031)ProstranBošković, Bogdan (7004055023)Bogdan (7004055023)Bošković2025-06-132025-06-132006https://doi.org/10.1016/j.pain.2006.04.023https://www.scopus.com/inward/record.uri?eid=2-s2.0-33749353714&doi=10.1016%2fj.pain.2006.04.023&partnerID=40&md5=20e59662241c817f6d473c4ee818bd62https://remedy.med.bg.ac.rs/handle/123456789/10882In this study, the effects of yohimbine (α 2 -adrenoceptor antagonist) and clonidine (α 2 -adrenoceptor agonist) on anti-hyperalgesia induced by carbamazepine and oxcarbazepine in a rat model of inflammatory pain were investigated. Carbamazepine (10-40 mg/kg; i.p.) and oxcarbazepine (40-160 mg/kg; i.p.) caused a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by concanavalin A (Con A, intraplantarly) in a paw pressure test in rats. Yohimbine (1-3 mg/kg; i.p.) significantly depressed the anti-hyperalgesic effects of carbamazepine and oxcarbazepine, in a dose- and time-dependent manner. Both drug mixtures (carbamazepine-clonidine and oxcarbazepine-clonidine) administered in fixed-dose fractions of the ED 50 (1/2, 1/4 and 1/8) caused significant and dose-dependent reduction of the hyperalgesia induced by Con A. Isobolographic analysis revealed a significant synergistic (supra-additive) anti-hyperalgesic effect of both combinations tested. These results indicate that anti-hyperalgesic effects of carbamazepine and oxcarbazepine are, at least partially, mediated by activation of adrenergic α 2 -receptors. In addition, synergistic interaction for anti-hyperalgesia between carbamazepine and clonidine, as well as oxcarbazepine and clonidine in a model of inflammatory hyperalgesia, was demonstrated. © 2006 International Association for the Study of Pain.CarbamazepineInflammatory hyperalgesiaOxcarbazepinePaw pressure testSynergistic interactionα ₂ -Adrenoceptors