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

Abstract

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 μg) of prostaglandin E 2. Dipyrone administered locally into the right hindpaw (50, 100 and 200 μg) 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 μg/paw) and tolbutamide (80, 160 and 320 μg/paw) antagonized the peripheral antinociception induced by dipyrone (200 μg/paw). Charybdotoxin (2 μg/ paw), a blocker of large conductance Ca 2+-activated K + channels, and dequalinium (50 μg/paw), a selective blocker of small conductance Ca 2+-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 μg) and 4-aminopyridine (100 μg) nor cesium (500 μg), 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.