Possible activation of inward rectifier- and G protein-coupled K + channels in the antinociception induced by non-steroidal anti-inflammatory drugs

Evidence suggests that ATP-sensitive-K + channels are important in the peripheral antinociceptive effect of some analgesics. Therefore, we sought to determine the participation of inward rectifier- and G protein-coupled K + -channels in the antinociceptive action of non-steroidal anti-inflammatory drugs (NSAIDs) in the formalin test. Female Wistar rats were injected into the dorsal surface of the right hind paw with 50 µl of diluted formalin inducing flinching behavior. Rats were pretreated with vehicle or increasing doses of NSAIDs before formalin administration. In order to determine if local antinociception was mediated by K + -channels, the effect of local pretreatment (10 min) with cesium, 4aminopiridyne and tetraethylammonium (inward rectifier- and G protein-coupled K + channel inhibitors) on the antinociceptive effect induced by NSAIDs was assessed. Administration of diclofenac, metamizol, meloxicam and indomethacin produced an antinociceptive effect only during the second phase of the test. Local pretreatment of the paw with the K + channel blockers dose-dependently prevented diclofenac-, metamizol- and meloxicam-induced antinociception, but not that of indomethacin. This result demonstrates the probable participation of the inward rectifier- and G protein-coupled K + channels in the antinociceptive effect of diclofenac, metamizol and meloxicam, but not of indomethacin.