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PAIN MEDICINE

The Contribution of Alpha-1 and Alpha-2 Adrenoceptors in Peripheral Imidazoline and Adrenoceptor Agonist-Induced Nociception

Ahmet Dogrul, MD, lke Coskun, and Tayfun Uzbay

From the Gülhane Military Medical Academy, Faculty of Medicine, Department of Medical Pharmacology, Psychopharmacology Research Unit, Ankara, Turkey.

Address correspondence and reprint requests to Ahmet Dogrul, MD, Gülhane Military Medical Academy, Faculty of Medicine, Department of Medical Pharmacology, Ankara, Turkey. Address e-mail to dogrula{at}gata.edu.tr.

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