Activation of ATP-sensitive K+ channels:: mechanism of peripheral antinociceptive action of the nitric oxide donor, sodium nitroprusside

Using the rat paw pressure test, in which sensitivity is increased by intraplantar injection of prostaglandin E-2 (PGE(2)), we conducted a study using several K+ channel blockers. The objective was to determine what types of K+ channels could be involved in the peripheral antinociceptive action of the nitric oxide donor sodium nitroprusside (SNP). SNP elicited a dose-dependent (250 and 500 mu g/paw) peripheral antinociceptive effect, which was considered local, since only higher doses produced an effect in the contralateral paw. The effect of SNP (500 mu g/paw) was dose-dependently antagonized by intraplantar administration of the sulfonylureas tolbutamide (20, 40 and 160 mu g) and glibenclamide (40, 80 and 160 mu g), selective blockers of ATP-sensitive K+ channels. Charybdotoxin (2 mu g/paw), a selective blocker of high conductance Ca2+-activated K+ channels, and apamin (10 mu g/paw), a selective blocker of low conductance Ca2+-activated K+ channels, did not modify the peripheral antinociception induced by SNP. Tetraethylammonium (2 mg/paw), 4-aminopyridine (200 mu g/paw) and cesium(800 mu g/paw) also had no effect. Based on this experimental evidence, we conclude that the activation of ATP-sensitive K+ channels could be the mechanism by which nitric oxide, donated by SNP, induces peripheral antinociception, and that Ca2+-activated K+ channels and voltage-dependent K+ channels appear not to be involved in the process. (C) 2000 Elsevier Science B.V. All rights reserved.