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 Ca2+-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.