Involvement of ATP-sensitive K+ channels in the peripheral antinociceptive effect induced by the α2-adrenoceptor agonist xylazine

Abstract

Xylazine is an α2-adrenergic agonist extensively used in veterinary medicine and animal experimentation for producing antinociception, sedation, and muscle relaxation. The nitric oxide (NO) / cGMP / ATP-sensitive K+ (KATP) channel pathway has been proposed as the action mechanism of peripheral antinociception of several groups of drugs, including opioids and nonsteroidal analgesics. Considering the lack of knowledge regarding the mechanisms involved in xylazine effects, the present study investigated the contribution of K+ channels on peripheral antinociception induced by xylazine using the rat paw pressure test, in which hyperalgesia was induced by intraplantar injection of prostaglandin E2. Xylazine administered into the right hind paw elicited a local antinociceptive effect, since only much higher doses produced a systemic effect in the contralateral paw. The peripheral antinociceptive effect induced by xylazine was antagonized by glibenclamide, a specific blocker of KATP channels. In another experiment, tetraethylammonium, a voltage-dependent K+-channel blocker, and paxilline and dequalinium, which are selective blockers for the large- and small-conductance Ca2+-activated K+ channels, respectively, were ineffective at blocking xylazine antinociception. These results provide evidence that the peripheral antinociceptive effect of xylazine probably results from KATP-channel activation, while the voltage-dependent K+ channels, small- and large-conductance Ca 2+-activated K+ channels, appear not to be involved in this mechanism. ©2009 The Japanese Pharmacological Society.