RESUMO
We examined the effect of several K+ channel blockers such as glibenclamide, tolbutamide, charybdotoxin (ChTX), apamin, tetraethylammonium chloride (TEA), 4-aminopyridine (4-AP), and cesium on the ability of fentanyl, a clinically used selective æ-opioid receptor agonist, to promote peripheral antinociception. Antinociception was measured by the paw pressure test in male Wistar rats weighing 180-250 g (N = 5 animals per group). Carrageenan (250 æg/paw) decreased the threshold of responsiveness to noxious pressure (delta = 188.1 ± 5.3 g). This mechanical hyperalgesia was reduced by fentanyl (0.5, 1.5 and 3 æg/paw) in a peripherally mediated and dose-dependent fashion (17.3, 45.3 and 62.6 percent, respectively). The selective blockers of ATP-sensitive K+ channels glibenclamide (40, 80 and 160 æg/paw) and tolbutamide (80, 160 and 240 æg/paw) dose dependently antagonized the antinociception induced by fentanyl (1.5 æg/paw). In contrast, the effect of fentanyl was unaffected by the large conductance Ca2+-activated K+ channel blocker ChTX (2 æg/paw), the small conductance Ca2+-activated K+ channel blocker apamin (10 æg/paw), or the non-specific K+ channel blocker TEA (150 æg/paw), 4-AP (50 æg/paw), and cesium (250 æg/paw). These results extend previously reported data on the peripheral analgesic effect of morphine and fentanyl, suggesting for the first time that the peripheral æ-opioid receptor-mediated antinociceptive effect of fentanyl depends on activation of ATP-sensitive, but not other, K+ channels.