title: alpha(2)-Adrenoceptor agonist xylazine induces peripheral antinociceptive effect by activation of the L-arginine/nitric oxide/cyclic GMP pathway in rat.
abstract: The L-arginine/nitric oxide/cyclic GMP pathway has been proposed as the mechanism of action for peripheral antinociception concerning several groups of drugs, including opioids and nonsteroidal analgesics. The aim of the present study was to investigate the involvement of the L-arginine/NO/cGMP pathway on antinociception induced by xylazine, an alpha(2)-adrenoceptor agonist extensively used in veterinary medicine and animal experimentation. The rat paw pressure test was used by inducing hyperalgesia via intraplantar injection of prostaglandin E(2) (2 microg). Xylazine was administered locally into the right hind paw (25, 50 and 100 microg) and either NO synthase inhibitor L-NOarg (12, 18 and 24 microg/paw), soluble guanylyl cyclase inhibitor ODQ (25, 50 and 100 microg/paw) or cGMP-phosphodiesterase inhibitor zaprinast (50 microg/paw) were previously administered to the right hind paw of Wistar rats. Xylazine administration elicited a local antinociceptive effect, since only much higher doses produce a systemic effect in the contralateral paw. The peripheral antinociceptive effect induced by xylazine (100 microg/paw) was antagonized by L-NOarg and by ODQ; however, zaprinast potentiated the antinociceptive effect of xylazine at 25 microg/paw. The results provide evidence that xylazine probably induces peripheral antinociceptive effect by L-arginine/NO/cGMP pathway activation.
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, ICB-UFMG, Belo Horizonte, MG, Brazil.
authors.forename: Thiago R L
authors.initials: TR
authors.lastname: Romero
authors.forename: Igor D G
authors.initials: ID
authors.lastname: Duarte
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects*; D000071756:Soluble Guanylyl Cyclase; D014991:Xylazine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000700:Analgesics; D004791:Enzyme Inhibitors; C000605667:Gucy1a2 protein, rat; D018160:Receptors, Cytoplasmic and Nuclear; D014991:Xylazine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D010727:Phosphoric Diester Hydrolases; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP