Dibutyryl-cyclic GMP induces peripheral antinociception via activation of ATP-sensitive K+ channels in the rat PGE(2)-induced hyperalgesic paw

1 Using the rat paw pressure test, in which increased sensitivity is induce d by intraplantar injection of prostaglandin E-2, we studied the action of several K+ channel blockers in order to determine what types of K+ channels could be involved in the peripheral antinociception induced by dibutyrylgu anosine 3: 5'-cyclic monophosphate (DbcGMP), a membrane permeable analogue of cyclic GMP. 2 DbcGMP elicited a dose-dependent (50. 75, 100 and 200 mug paw(-1)) periph eral antinociceptive effect. The effect of the 100 pg dose of DbcGMP was co nsidered to be local since only a higher dose (300 mug paw(-1)) produced an tinociception in the contralateral paw. 3 The antinociceptive effect of DbcGMP (100 mug paw(-1)) was dose-dependent ly antagonized by intraplantar administration of the sulphonylureas tolbuta mide (20. 40 and 160 mug) and glibenclamide (40, 80 and 160 mug), selective blockers of ATP-sensitive K+ channels. 4 Charybdotoxin (2 mug paw(-1)), a selective blocker of high conductance Ca 2+-activated K+ channels, and apamin (10 mug paw(-1)), a selective blocker of low conductance Ca2+-activated K+ channels, did not modify the periphera l antinociception induced by DbcGMP. 5 Tetraethylammonium (2 mg paw(-1)), 4-aminopyridine (200 mug paw(-1)) and cesium (800 paw(-1)), non-selective voltage-gated potassium channel blocker s, also had no effect. 6 Based on this experimental evidence. we conclude that the activation of A TP-sensitive K+ channels could be the mechanism by which DbcGMP induces per ipheral anti nociception, and that Ca2+ activated K+ channels and voltage-d ependent K+ channels appear not to be involved in the process.