Role of alpha 2-adrenoceptors in the local peripheral antinociception by carbamazepine in a rat model of inflammatory mechanical hyperalgesia
No Thumbnail
Authors
Vučković, Sonja M.Tomić, Maja

Stepanović-Petrović, Radica

Ugrešić, Nenad
Prostran, Milica

Bošković, Bogdan
Article (Published version)

Metadata
Show full item recordAbstract
The anticonvulsant carbamazepine was recently shown to possess local peripheral antinociceptive properties. In this study, we investigated whether alpha 2-adrenergic receptors are involved in the local peripheral antihyperalgesic effects of carbamazepine and determined the type of interaction between carbamazepine and clonidine, an alpha 2-adrenoceptor agonist. Intraplantar (i.pl.) coadministration of either carbamazepine (100-1000 nmol/paw) or clonidine (1.9-3.7 nmol/paw) with the proinflammatory compound concanavalin A (Con A; 0.8 mg/paw) caused a significant dose- and time-dependent reduction of the difference between the forces exerted by a rat's hind paws in a modified paw-pressure test. The coadministration of 260 and 520 nmol/paw (i.pl.) yohimbine, an alpha 2-adrenoceptor antagonist, with carbamazepine, significantly depressed the local antihyperalgesic effect in a dose- and time-dependent manner whereas yohimbine by itself did not have any effect. The administration of a mixtur...e of carbamazepine and clonidine at fixed dose fractions (114, 112 and 314) of ED50 caused a significant and dose-dependent reduction of Con A-induced hyperalgesia. Isobolographic analysis revealed an additive interaction. These results suggest that alpha 2-adrenoceptors play a role in the local peripheral antihyperalgesic effects of carbamazepine and that local peripheral coadministration of carbamazepine with clonidine results in an additive antihyperalgesic effect.
Keywords:
additive interaction / carbamazepine / clonidine / inflammatory hyperalgesia / isobolographic analysis / local administration / peripheral alpha 2-adrenoceptors / yohimbineSource:
Methods and Findings in Experimental and Clinical Pharmacology, 2007, 29, 10, 689-696Publisher:
- Prous Science, Sa, Barcelona
DOI: 10.1358/mf.2007.29.10.1147773
ISSN: 0379-0355
PubMed: 18200332