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 (alpha-2 AR agonist), agmatine (imidazoline receptor and alpha-2 AR agonist), noradrenaline (mixed alpha-1 and alpha-2 AR agonist), phenylephrine (alpha-1 AR agonist), or 0.9% saline was given by intradermal injection (10 microL) into the tail. The intradermal injection of clonidine (1, 3, and 10 microg) and agmatine (3, 30, and 50 microg) produced dose-dependent antinociception, whereas noradrenaline (1, 10, and 30 microg) and phenylephrine (1, 10 and 30 microg) produced dose-dependent thermal hyperalgesia. Clonidine (10 microg) and agmatine (50 microg)-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 microg) and phenylephrine (30 mug)-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.
Dogrul
Ahmet
A
Gülhane Military Medical Academy, Faculty of Medicine, Department of Medical Pharmacology, Ankara, Turkey. dogrula@gata.edu.tr
Coskun
Ilke
I
Uzbay
Tayfun
T
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000376:Agmatine / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000188:drug therapy; D054755:Imidazoline Receptors; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D011955:Receptors, Drug / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000700:Analgesics; D054755:Imidazoline Receptors; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; D010656:Phenylephrine; D015016:Yohimbine; D000376:Agmatine; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin