GABAergic mechanisms in antinociception.

GABAergic mechanisms appear to be involved in antinociceptive processes. Generally, peripheral administration of GABAergic agents increases the antinociceptive effect of morphine, but central administration inhibits this effect, suggesting that multiple interactions may occur. GABAergic agents also can produce antinociception directly. Muscimol and THIP (GABAA agonists) act at supraspinal sites to produce antinociception, but do not appear to interact with bicuculline sensitive receptors. Baclofen (a GABAB agonist) acts at both supraspinal and spinal sites. Supraspinal mechanisms include inhibition of ascending noradrenergic and dopaminergic pathways but activation of descending noradrenergic pathways. The spinal mechanism may involve postsynaptic inhibition of the effect of substance P. D-Baclofen is an antagonist at spinal baclofen receptors. Antinociception produced by inhibitors of GABA-transaminase is not reduced by bicuculline in most studies, while manipulations which increase the antinociceptive effect of baclofen do not alter or block the effect of GABA-transaminase inhibitors. An understanding of the role of GABAA and GABAB receptors in antinociception will require clarification of some curious pharmacological actions of bicuculline and the use of a specific GABAB receptor antagonist.