Pharmacological mechanisms involved in the antinociceptive effects of dexmedetomidine in mice

Detalhes bibliográficos
Autor(a) principal: Rangel, Rafael A. S
Data de Publicação: 2014
Outros Autores: Marinho, Bruno G, Fernandes, Patrícia D, Moura, Roberto S, de, Lessa, Marcos A
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/10606
Resumo: Universidade do Estado do Rio de Janeiro. Departamento de Farmacologia e Psicobiologia. Rio de Janeiro, RJ, Brasil.
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spelling Rangel, Rafael A. SMarinho, Bruno GFernandes, Patrícia DMoura, Roberto S, deLessa, Marcos A2015-06-01T19:34:21Z2015-06-01T19:34:21Z2014RANGEL, Rafael A. S. et al. Pharmacological mechanisms involved in the antinociceptive effects of dexmedetomidine in mice. Fundamental & Clinic Pharmacology, v.28, n.1, p.104-113, feb. 2014.1472-82-6https://www.arca.fiocruz.br/handle/icict/1060610.1111/j.1472-8206.2012.01068.xengWiley Online LibraryPharmacological mechanisms involved in the antinociceptive effects of dexmedetomidine in miceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade do Estado do Rio de Janeiro. Departamento de Farmacologia e Psicobiologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Programa de Desenvolvimento de Fármacos. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Programa de Desenvolvimento de Fármacos. Rio de Janeiro, RJ, BrasilUniversidade do Estado do Rio de Janeiro. Departamento de Farmacologia e Psicobiologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Investigação Cardiovascular. Rio de Janeiro, RJ, Brasil.Dexmedetomidine (DEX) is a α2-adrenoceptor (α2-AR) agonist used as an anesthetic adjuvant and as sedative in critical care settings. Typically, α2-AR agonists release nitric oxide (NO) and subsequently activate NO-GMPc pathway and have been implicated with antinociception. In this study, we investigate the pharmacological mechanisms involved in the antinociceptive effects of DEX, using an acetic acid-induced writhing assay in mice. Saline or DEX (1, 2, 5, or 10 μg/kg) was intravenously injected 5 min before ip administration of acetic acid and the resulting abdominal constrictions were then counted for 10 min. To investigate the possible mechanisms related to antinociceptive effect of DEX (10 μg/kg), the animals were also pretreated with one of the following drugs: 7-nitroindazole (7-NI; 30 mg/kg ip); 1H-[1,2,4] oxadiazole [4,3-a] quinoxaline-1-one (ODQ; 2.5 mg/kg, ip); yohimbine (YOH; 1 mg/kg, ip); atropine (ATRO; 2 mg/kg, ip); glibenclamide (GLIB; 1 mg/kg, i.p.) and naloxone (NAL; 0.2 mg/kg, ip). A rotarod and open-field performance test were performed with DEX at 10 μg/kg dose. DEX demonstrated its potent antinociceptive effect in a dose-dependent manner. The pretreatment with 7-NI, ODQ, GLIB, ATRO, and YOH significantly reduced the antinociceptive affects of DEX. However, NAL showed no effecting DEX-induced antinociception. The rotarod and open-field tests confirmed there is no detectable sedation or even significant motor impairment with DEX at 10 μg/kg dose. Our results suggest that the α2-AR and NO-GMPc pathways play important roles in the systemic antinociceptive effect of DEX in a murine model of inflammatory pain. Furthermore, the antinociceptive effect exerted by DEX appears to be dependent on KATP channels, independent of opioid receptor activity.AntinociceptionDexmedetomidinePainNitric oxideÓxido NítricoDexmedetomidinaDorinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txttext/plain1914https://www.arca.fiocruz.br/bitstream/icict/10606/1/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD51ORIGINALmarcos_lessa2etal_IOC_2014.pdfapplication/pdf337544https://www.arca.fiocruz.br/bitstream/icict/10606/2/marcos_lessa2etal_IOC_2014.pdf63463e8807ca0e74db3e2306c0569cc9MD52TEXTmarcos_lessa2etal_IOC_2014.pdf.txtmarcos_lessa2etal_IOC_2014.pdf.txtExtracted texttext/plain41932https://www.arca.fiocruz.br/bitstream/icict/10606/3/marcos_lessa2etal_IOC_2014.pdf.txt3e3b0ce6c280102105a712c5e7f24d75MD53icict/106062022-06-24 13:10:42.05oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352022-06-24T16:10:42Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv Pharmacological mechanisms involved in the antinociceptive effects of dexmedetomidine in mice
title Pharmacological mechanisms involved in the antinociceptive effects of dexmedetomidine in mice
spellingShingle Pharmacological mechanisms involved in the antinociceptive effects of dexmedetomidine in mice
Rangel, Rafael A. S
Antinociception
Dexmedetomidine
Pain
Nitric oxide
Óxido Nítrico
Dexmedetomidina
Dor
title_short Pharmacological mechanisms involved in the antinociceptive effects of dexmedetomidine in mice
title_full Pharmacological mechanisms involved in the antinociceptive effects of dexmedetomidine in mice
title_fullStr Pharmacological mechanisms involved in the antinociceptive effects of dexmedetomidine in mice
title_full_unstemmed Pharmacological mechanisms involved in the antinociceptive effects of dexmedetomidine in mice
title_sort Pharmacological mechanisms involved in the antinociceptive effects of dexmedetomidine in mice
author Rangel, Rafael A. S
author_facet Rangel, Rafael A. S
Marinho, Bruno G
Fernandes, Patrícia D
Moura, Roberto S, de
Lessa, Marcos A
author_role author
author2 Marinho, Bruno G
Fernandes, Patrícia D
Moura, Roberto S, de
Lessa, Marcos A
author2_role author
author
author
author
dc.contributor.author.fl_str_mv Rangel, Rafael A. S
Marinho, Bruno G
Fernandes, Patrícia D
Moura, Roberto S, de
Lessa, Marcos A
dc.subject.en.pt_BR.fl_str_mv Antinociception
Dexmedetomidine
Pain
Nitric oxide
topic Antinociception
Dexmedetomidine
Pain
Nitric oxide
Óxido Nítrico
Dexmedetomidina
Dor
dc.subject.decs.pt_BR.fl_str_mv Óxido Nítrico
Dexmedetomidina
Dor
description Universidade do Estado do Rio de Janeiro. Departamento de Farmacologia e Psicobiologia. Rio de Janeiro, RJ, Brasil.
publishDate 2014
dc.date.issued.fl_str_mv 2014
dc.date.accessioned.fl_str_mv 2015-06-01T19:34:21Z
dc.date.available.fl_str_mv 2015-06-01T19:34:21Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv RANGEL, Rafael A. S. et al. Pharmacological mechanisms involved in the antinociceptive effects of dexmedetomidine in mice. Fundamental & Clinic Pharmacology, v.28, n.1, p.104-113, feb. 2014.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/10606
dc.identifier.issn.pt_BR.fl_str_mv 1472-82-6
dc.identifier.doi.pt_BR.fl_str_mv 10.1111/j.1472-8206.2012.01068.x
identifier_str_mv RANGEL, Rafael A. S. et al. Pharmacological mechanisms involved in the antinociceptive effects of dexmedetomidine in mice. Fundamental & Clinic Pharmacology, v.28, n.1, p.104-113, feb. 2014.
1472-82-6
10.1111/j.1472-8206.2012.01068.x
url https://www.arca.fiocruz.br/handle/icict/10606
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dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
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