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PAIN MECHANISMS

The Involvement of Peripheral ₂-Adrenoceptors in the Antihyperalgesic Effect of Oxcarbazepine in a Rat Model of Inflammatory Pain

Maja A. Tomi, BPharm, MSc^*, Sonja M. Vukovi, MD, PhD, Radica M. Stepanovi-Petrovi, BPharm, PhD^*, Nenad D. Ugrei, BPharm, PhD^*, Sonja Lj Paranos, BPharm^*, Milica Prostran, MD, PhD, and Bogdan Bokovi, BPharm, MD, PhD

From the *Department of Pharmacology, Faculty of Pharmacy, Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; and Medical Military Academy, Belgrade, Serbia.

Address correspondence and reprint requests to Maja A. Tomi, BPharm, MSc, Department of Pharmacology, Faculty of Pharmacy, Vojvode Stepe 450, POB 146, 11221 Belgrade, Serbia. Address e-mail to majat{at}pharmacy.bg.ac.yu.

Abstract

BACKGROUND: We studied whether peripheral ₂-adrenergic receptors are involved in the antihyperalgesic effects of oxcarbazepine by examining the effects of yohimbine (selective ₂-adrenoceptor antagonist), BRL 44408 (selective _2A-adrenoceptor antagonist), MK-912 (selective _2C-adrenoceptor antagonist), and clonidine (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.), 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 ED₅₀ (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.

CONCLUSIONS: Our results indicate that the peripheral _2A and _2C adrenoceptors could be involved in the antihyperalgesic effects of oxcarbazepine in a rat model of inflammatory hyperalgesia.

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				R. M. Stepanovic-Petrovic, M. A. Tomic, S. M. Vuckovic, S. Paranos, N. D. Ugresic, M. S. Prostran, S. Milovanovic, and B. Boskovic The Antinociceptive Effects of Anticonvulsants in a Mouse Visceral Pain Model Anesth. Analg., June 1, 2008; 106(6): 1897 - 1903. [Abstract] [Full Text] [PDF]