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alpha(2)-Adrenoceptor agonist xylazine induces peripheral antinociceptive effect by activation of the L-arginine/nitric oxide/cyclic GMP pathway in rat.
Eur J Pharmacol. 2009 Jun 24; 613(1-3):64-7.EJ

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+Show Affiliations

Department of Pharmacology, Institute of Biological Sciences, ICB-UFMG, Belo Horizonte, MG, Brazil.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19389395

Citation

Romero, Thiago R L., and Igor D G. Duarte. "Alpha(2)-Adrenoceptor Agonist Xylazine Induces Peripheral Antinociceptive Effect By Activation of the L-arginine/nitric Oxide/cyclic GMP Pathway in Rat." European Journal of Pharmacology, vol. 613, no. 1-3, 2009, pp. 64-7.
Romero TR, Duarte ID. Alpha(2)-Adrenoceptor agonist xylazine induces peripheral antinociceptive effect by activation of the L-arginine/nitric oxide/cyclic GMP pathway in rat. Eur J Pharmacol. 2009;613(1-3):64-7.
Romero, T. R., & Duarte, I. D. (2009). Alpha(2)-Adrenoceptor agonist xylazine induces peripheral antinociceptive effect by activation of the L-arginine/nitric oxide/cyclic GMP pathway in rat. European Journal of Pharmacology, 613(1-3), 64-7. https://doi.org/10.1016/j.ejphar.2009.04.031
Romero TR, Duarte ID. Alpha(2)-Adrenoceptor Agonist Xylazine Induces Peripheral Antinociceptive Effect By Activation of the L-arginine/nitric Oxide/cyclic GMP Pathway in Rat. Eur J Pharmacol. 2009 Jun 24;613(1-3):64-7. PubMed PMID: 19389395.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - alpha(2)-Adrenoceptor agonist xylazine induces peripheral antinociceptive effect by activation of the L-arginine/nitric oxide/cyclic GMP pathway in rat. AU - Romero,Thiago R L, AU - Duarte,Igor D G, Y1 - 2009/04/21/ PY - 2009/02/09/received PY - 2009/03/30/revised PY - 2009/04/08/accepted PY - 2009/4/25/entrez PY - 2009/4/25/pubmed PY - 2009/8/29/medline SP - 64 EP - 7 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 613 IS - 1-3 N2 - 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. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/19389395/alpha_2__Adrenoceptor_agonist_xylazine_induces_peripheral_antinociceptive_effect_by_activation_of_the_L_arginine/nitric_oxide/cyclic_GMP_pathway_in_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(09)00361-6 DB - PRIME DP - Unbound Medicine ER -