CLONIDINE INDUCED ANTINOCICEPTION; BIOCHEMICAL AND CELLULAR EVIDENCES ON THE MECHANISM OF ACTION

Objectives: To examine the role of blood glucose changes (biochemical) and the ATP sensitive potassium channels (cellular) on clonidine induced antinociception in normal (non-diabetic) mice. Methods: Swiss male albino mice (20-25 g) were employed. Blood glucose was estimated by AMES Glucometer and the antinociception by acetic acid induced abdominal constrictions assay. The effect of clonidine (1 .10 or 20 µg/kg; i.p 15 min. prior) on these parameters was measured. The effect of glibenclamide per se (10 mg/kg; i.p) and on clonidine (1 or 10 µg/kg) induced changes (given 10 min. prior to clonidine) was recorded. Further, the effect of either yohimbine (1 mg/kg; i.p.) or naloxone (10 mg/kg; i.p.) per se and on the effect of combined exposure with glibenclamide and clonidine induced changes on the above parameters were also recorded. Results: Clonidine produced hyperglycemia almost uniformly irrespective of the doses tested. However, its antinociceptive response was dose related. Glibenclamide perse (10 mg/kg; i.p) induced hypoglycemia without any antinociceptive response. Its pretreatment reversed the hyperglycemic effect and enhanced the antinociceptive response of clonidine. Yohimbine but not naloxone attenuated glibenclamide induced enhancement of clonidine induced antinociceptive response. Conclusion: The findings indicate that clonidine induced antinociception is independent of its hyperglycemic action. In contrast to morphine, clonidine induced antinociception seems not to involve ATP sensitive potassium channels, rather its antinociception is enhanced by the blockade of these channels. This enhancement is attributed partially to a adrenergic mechanisms excluding the opioid pathways. The results favour the contention that the mecKanisms involved in the antinociception induced by clonidine and morphine are different.