Involvement of ATP-sensitive K+ channels in the peripheral antinociceptive effect induced by dipyrone

We evaluated the effect of several K+ channel blockers on the peripheral antinociception induced by dipyrone using the rat paw, pressure test, in which sensitivity is increased by intraplantar injection (2 mug) of prostaglandin E-2. Dipyrone administered locally into the right hindpaw (50, 100 and 200 mug) 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 specific blockers of ATP-sensitive K+ channels glibenclamide (40, 80 and 160 mug/paw) and tolbutamide (80, 160 and 320 mug/paw) antagonized the peripheral antinociception induced by dipyrone (200 mug/paw). Charybdotoxin (2 mug/paw), a blocker of large conductance Ca2+-activated K+ channels, and dequalinium (50 mug/paw), a selective blocker of small conductance Ca2+-activated K+ channels, did not modify the effect of dipyrone. This effect was also unaffected neither by intraplantar administration of non-specific voltage-dependent K+ channel blockers tetraethylammonium (1700 mug) and 4-aminopyridine (100 mug) nor cesium (500 mug), a non-specific K+ channel blocker. These results suggest that the peripheral antinociceptive effect of dipyrone may result from activation of ATP-sensitive K+ channels, while other K+ channels appear not to be involved in the process. (C) 2002 Elsevier Science B.V All rights reserved.