The contribution of alpha-1 and alpha-2 adrenoceptors in peripheral imidazoline and adrenoceptor agonist-induced nociception

We evaluated the effects of activation of peripheral adrenoceptors (AR) and imidazoline receptors on nociception and the contribution of alpha-1 and alpha-2 AR receptors in agonist-induced nociception by using the tail-flick test in mice. Clonidine (a-2 AR agonist), agmatine (imidazoline receptor and a-2 AR agonist), noradrenaline (mixed a-1 and a-2 AR agonist), phenylephrine (a-1 AR agonist), or 0.9% saline was given by intradermal injection (10 mu L) into the tail. The intradermal injection of clonidine (1, 3, and 10 mu g) and agmatine (3, 30, and 50 mu g) produced dose-dependent antinociception, whereas noradrenaline (1, 10, and 30 mu g) and phenylephrine (1, 10 and 30 kg) produced dose-dependent thermal hyperalgesia. Clonidine (10 mu g) and agmatine (50 mu g)-induced peripheral antinociception were antagonized by pretreatment with yohimbine (2.5 mg/kg IP), a selective alpha-2 AR antagonist, but not by prazosin (1 mg/kg IP), a selective alpha-1 AR antagonist. Noradrenaline (30 mu g) and phenylephrine (30 mu g)-induced thermal hyperalgesia were antagonized by prazosin (1 mg/kg IP) but not by yohimbine (2.5 mg/kg IP). Our results suggest that local thermal hyperalgesic effects of noradrenaline and phenylephrine are linked to alpha-1 AR and the peripheral antinociceptive action of clonidine and agmatine are linked to alpha-2 AR.