Involvement of ATP-sensitive K(+) channels in the peripheral antinociceptive effect induced by ketamine.

OBJECTIVE

To investigate the contribution of K(+) channels on peripheral antinociception induced by ketamine.

STUDY DESIGN

Prospective experimental study.

ANIMALS

110 male Wistar rats weighing 160-200 g.

METHODS

The paw pressure required to elicit limb flexion was designated as the nociceptive threshold. Hyperalgesia was induced by intraplantar injection of prostaglandin E2 . All drugs were administered locally into the right hind paw of rats. Ketamine was administered into the right hind paw 2 hours and 55 minutes after local injection of PGE2 . Tetraethylammonium was administered 30 minutes prior to ketamine and the other K(+) channel blockers, glibenclamide, dequalinium and paxilline, were administered 5 minutes prior to ketamine.

RESULTS

Prostaglandin E2 (2 μg per paw) induced hyperalgesia. Ketamine (10, 20, 40 and 80 μg per paw) elicited a local peripheral antinociceptive effect that was antagonized by a specific blocker of ATP-sensitive K(+) channels, glibenclamide (20, 40 and 80 μg per paw). In another experiment, the non-selective voltage-dependent K(+) channel blocker tetraethylammonium (30 μg per paw) and small and large conductance blockers of Ca(2+) -activated K(+) channels, dequalinium (50 μg per paw) and paxilline (20 μg per paw), were ineffective at blocking the effect of a local ketamine injection.

CONCLUSIONS AND CLINICAL RELEVANCE

Analysis of these results provides evidence that ketamine, may in part, induce peripheral antinociceptive effects by ATP-sensitive K(+) channel pathway activation.