GABAergic mechanisms are involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia

Background/Aims: 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. Conclusion: 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. Copyrigh