N-palmitoyl-ethanolamine (PEA) induces peripheral antinociceptive effect by ATP-sensitive K +-channel activation

Although the antinociceptive effects of n-palmitoyl-ethanolamine (pea) were first characterized nearly 50 years ago,the identity of the mechanism that mediates these actions has not been elucidated. the present study investigated the contribution of k + channels on peripheral antinociception induced by the cb 2 agonist pea. nociceptive thresholds to mechanical paw stimulation of wistar rats treated with intraplantar prostaglandin e 2 to induce hyperalgesia were measured,and other agents were also given by local injection. pea (5,10,and 20 μg/paw) elicited a local peripheral antinociceptive effect. this effect was antagonized by glibenclamide,a selective blocker of atp-sensitive k + channels (20,40,and 80 μg/paw). in addition,neither the voltage-dependent k + channel-specific blocker tetraethylammonium (30 μg/paw) nor the small and large conductance blockers of ca 2+-activated k + channels,dequalinium (50 μg/paw) and paxilline (20 μg/paw),respectively,were able to block the local antinociceptive effect of pea. these results indicate that the activation of atp-sensitive k + channels could be the mechanism that induces peripheral antinociception by pea and that voltage-dependent k + channels and small and large conductance ca 2+-activated k + channels do not appear to be involved in this mechanism. © the japanese pharmacological society.