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

Abstract

BACKGROUND:

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.

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 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.

CONCLUSIONS:

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.

• Authors: Maja A Tomić, Sonja M Vucković, Radica M Stepanović-Petrović, Nenad D Ugresić, Sonja Lj Paranos, Milica S Prostran, Bogdan Bosković
• Journal: Anesthesia and analgesia (Anesth Analg) Vol. 105 Issue 5 Pg. 1474-81, table of contents (Nov 2007) ISSN: 1526-7598 [Electronic] United States
• PMID: 17959985 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic alpha-2 Receptor Agonists
• Receptors, Adrenergic, alpha-2
• Carbamazepine
• Clonidine
• Oxcarbazepine

Topics

• Adrenergic alpha-2 Receptor Agonists
• Animals
• Carbamazepine (analogs & derivatives, pharmacology, therapeutic use)
• Clonidine (pharmacology, therapeutic use)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Hyperalgesia (drug therapy, physiopathology)
• Inflammation (drug therapy, physiopathology)
• Male
• Oxcarbazepine
• Pain (drug therapy, physiopathology)
• Rats
• Rats, Wistar
• Receptors, Adrenergic, alpha-2 (physiology)