| 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
(Affiliation: Department of Pharmacology, Faculty of Pharmacy, Faculty of Medicine, University of Belgrade, Belgrade, Serbia. majat at pharmacy.bg.ac.yu)
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| Journal | Anesthesia and analgesia
(Anesth Analg)
Vol. 105
Issue 5
Pg. 1474-81, table of contents
(Nov 2007)
ISSN: 1526-7598 United States |
| PMID | 17959985
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Receptors, Adrenergic, alpha-2
- oxcarbazepine
- Carbamazepine
- Clonidine
|
| Topics |
- 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
- Pain
(drug therapy, physiopathology)
- Rats
- Rats, Wistar
- Receptors, Adrenergic, alpha-2
(agonists, physiology)
|
