GABAergic mechanisms are involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia.
OBJECTIVE
The purpose of this study was to investigate the involvement of GABAergic mechanisms in the antihyperalgesic effect of carbamazepine and oxcarbazepine by examining the effect of bicuculline (GABA(A) receptor antagonist) on these effects of antiepileptic drugs.


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 carbamazepine/oxcarbazepine on Con A-induced hyperalgesia, and (3) the effects of bicuculline on the carbamazepine/oxcarbazepine antihyperalgesia.


RESULTS
Intraperitoneally injected bicuculline (0.5-1 mg/kg, i.p.) exhibited significant suppression of the systemic antihyperalgesic effects of carbamazepine (27 mg/kg, i.p.) and oxcarbazepine (80 mg/kg, i.p.). When applied intraplantarly, bicuculline (0.14 mg/paw, i.pl.) did not produce any change in the peripheral antihyperalgesic effects of carbamazepine (0.14 mg/paw, i.pl.) and oxcarbazepine (0.5 mg/paw, i.pl.). Bicuculline alone did not produce an intrinsic effect in the paw-pressure test.


CONCLUSIONS
These results indicate that the antihyperalgesic effects of carbamazepine and oxcarbazepine against inflammatory hyperalgesia involve in part the GABAergic inhibitory modulation of pain transmission at central, but not at peripheral sites, which is mediated via GABA(A) receptor activation.
Stepanović-Petrović
Radica M
RM
Department of Pharmacology, Faculty of Pharmacy, Belgrade, Serbia. racabbr@eunet.yu
Tomić
Maja A
MA
Vucković
Sonja M
SM
Kocev
Nikola
N
Ugresić
Nenad D
ND
Prostran
Milica S
MS
Bosković
Bogdan
B
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003208:Concanavalin A; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D007274:Injections, Intraperitoneal; D008297:Male; D000078330:Oxcarbazepine; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D018712:Analgesics, Non-Narcotic; D000927:Anticonvulsants; D018756:GABA Antagonists; D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D003208:Concanavalin A; D002220:Carbamazepine; D000078330:Oxcarbazepine; D001640:Bicuculline