We investigated the effect of
chloride and
potassium channel blockers on the antinociception induced by
GABA(C) receptor agonist
CACA (cis-4-aminocrotonic acid) using the paw pressure test, in which
pain sensitivity was increased by an intraplantar injection (2 microg) of
prostaglandin E(2) (
PGE(2)).
CACA administered locally into the right hindpaw (25, 50 and 100 microg/paw) elicited a dose-dependent antinociceptive effect which was demonstrated to be local, since only higher doses produced an effect when injected in the contralateral paw. The
GABA(C) receptor antagonist (1,2,5,6 tetrahydropyridin-4-yl)
methylphosphinic acid (TPMPA; 5, 10 and 20 microg/paw) antagonized, in a dose-dependent manner, the peripheral antinociception induced by
CACA (100 microg), suggesting a specific effect. This effect was reversed by the
chloride channel coupled receptor blocker
picrotoxin (0.8 microg/paw).
Glibenclamide (160 microg) and
tolbutamide (320 microg), blockers of
ATP-sensitive potassium channels,
charybdotoxin (2 microg), a large-conductance
potassium channel blocker,
dequalinium (50 microg), a small-conductance
potassium channel blocker, and
cesium (500 microg), a non-specific
potassium channel blocker did not modify the peripheral antinociception induced by
CACA. This study provides evidence that activation of
GABA(C) receptors in the periphery induces antinociception, that this effect results from the activation of
chloride channel coupled
GABA(C) receptors and that
potassium channels appear not to be involved.