δ-Opioid receptor agonist SNC80 induces peripheral antinociception via activation of ATP-sensitive K+ channels

We investigated the effect of several K+ channel blockers on the antinociception induced by δ-opioid receptor agonist SNC80 using the paw pressure test, in which pain sensitivity is increased by an intraplantar injection (2 μg) of prostaglandin E2 (PGE2). Administration of SNC80 (20, 40 and 80 μg/paw) caused a decrease in the hyperalgesia induced by PGE2, in a dose-dependent manner. The possibility of higher dose of SNC80 (80 μg) causing a central or systemic effect was excluded since administration of the drug into the contralateral paw did not elicit antinociception in the right paw. Specific blockers of ATP-sensitive K+ channels, glibenclamide (20, 40 and 80 μg/paw) and tolbutamide (40, 80 and 160 μg/paw), antagonized the peripheral antinociception induced by SNC80 (80 μg). On the other hand, charybdotoxin (2 μg/paw), a large-conductance blocker of Ca2+-activated K+ channels, and dequalinium (50 μg/paw), a small conductance selective blocker of Ca2+-activated K+ channels, did not modify the effect of SNC80. This effect also remained unaffected by intraplantar administration of the voltage-dependent K+ channel blockers tetraethylammonium (30 μg/paw) and 4-aminopyridine (10 μg/paw), and of a non-specific K+ channel blocker, cesium (500 μg/paw). This study provides evidence that the peripheral antinociceptive effect of SNC80 result from the activation of ATP-sensitive K+ channels, and the other K+ channels are not involved.