Evidence for participation of GABA(A) receptors in a rat model of secondary hyperalgesia.

We investigated the involvement of endogenous gamma-aminobutyric acid (GABA) in the modulation of secondary hyperalgesia induced by intraplantar (i.pl.) injection of 5% formalin in the rat tail-flick test. Intraplantar injection of gabamimetic drugs such as gabapentin (150-600 microg/site) or phenobarbital (20-80 microg/site) reversed secondary hyperalgesia, as measured by an increase in the tail-flick latency, thus displaying a peripheral antihyperalgesic effect. Central inhibition of the secondary hyperalgesia response by gabapentin was obtained following injection of either 200 microg intrathecally (i.t.) or 50 mg intraperitoneally (i.p.). The effects induced by gabamimetics were blocked locally or centrally by prior treatment with the specific GABA(A) receptor antagonist, bicuculline (80 ng/paw or 20 ng, i.t.). These data indicate the participation of endogenous GABA in the modulation of secondary hyperalgesia, through either a peripheral and/or a central action. They also indicate that GABA(A) receptors might be involved since a specific antagonist of these receptors (bicuculline) blocked this response.