Author | Zarpelon, Ana Carla | |
Author | Souza, Guilherme R. | |
Author | Cunha, Thiago M. | |
Author | Schivo, Ieda R.S. | |
Author | Marchesi, Mario | |
Author | Casagrande, Rubia | |
Author | Pinge-Filho, Phileno | |
Author | Cunha, Fernando Q. | |
Author | Ferreira, Sergio H. | |
Author | Miranda, Katrina M. | |
Author | Verri Jr, Waldiceu Aparecido | |
Access date | 2016-09-30T19:38:48Z | |
Available date | 2016-09-30T19:38:48Z | |
Document date | 2013 | |
Citation | ZARPELON, Ana Carla et al. The nitroxyl donor, Angeli’s salt, inhibits inflammatory hyperalgesia in rats. Neuropharmacology, n. 71, p. 1-9, 2013. | pt_BR |
ISSN | 0028-3908 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/16029 | |
Sponsorship | CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), Fundação
Araucária, FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo), CAPES (Coordenação de
Aperfeiçoamento de Pessoal de Nível Superior), Decit/SCTIE/MS | pt_BR |
Language | eng | pt_BR |
Publisher | Bruno Frenguelli | pt_BR |
Rights | open access | pt_BR |
Title | The nitroxyl donor, Angeli’s salt, inhibits inflammatory hyperalgesia in rats | pt_BR |
Type | Article | pt_BR |
DOI | 10.1016/j.neuropharm.2013.03.009 | pt_BR |
Abstract | Nitric oxide modulates pain development. However, there is no evidence on the effect of nitroxyl (HNO/NO⁻) in nociception. Therefore, we addressed whether nitroxyl inhibits inflammatory hyperalgesia and its mechanism using the nitroxyl donor Angeli's salt (AS; Na₂N₂O₃). Mechanical hyperalgesia was evaluated using a modified Randall and Selitto method in rats, cytokine production by ELISA and nitroxyl was determined by confocal microscopy in DAF (a cell permeable reagent that is converted into a fluorescent molecule by nitrogen oxides)-treated dorsal root ganglia neurons in culture. Local pre-treatment with AS (17-450 μg/paw, 30 min) inhibited the carrageenin-induced mechanical hyperalgesia in a dose- and time-dependent manner with maximum inhibition of 97%. AS also inhibited carrageenin-induced cytokine production. AS inhibited the hyperalgesia induced by other inflammatory stimuli including lipopolysaccharide, tumor necrosis factor-α, interleukin-1β and prostaglandin E2. Furthermore, the analgesic effect of AS was prevented by treatment with ODQ (a soluble guanylate cyclase inhibitor), KT5823 (a protein kinase G [PKG] inhibitor) or glybenclamide (an ATP-sensitive K⁺ channel blocker), but not with naloxone (an opioid receptor antagonist). AS induced concentration-dependent increase in fluorescence intensity of DAF-treated neurons in a l-cysteine (nitroxyl scavenger) sensitive manner. l-cysteine did not affect the NO⁺ donor S-Nitroso-N-acetyl-DL- penicillamine (SNAP)-induced anti-hyperalgesia or fluorescence of DAF-treated neurons. This is the first study to demonstrate that nitroxyl inhibits inflammatory hyperalgesia by reducing cytokine production and activating the cGMP/PKG/ATP-sensitive K⁺ channel signaling pathway in vivo. | pt_BR |
Affilliation | Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Patologia. Londrina, PR, Brasil. | pt_BR |
Affilliation | Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil. | pt_BR |
Affilliation | Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil. | pt_BR |
Affilliation | Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil. | pt_BR |
Affilliation | University of Arizona. Department of Chemistry and Biochemistry. Tucson, Arizona, USA. | En |
Affilliation | Universidade Estadual de Londrina. Hospital Universitário (Centro de Ciências da Saúde). Departamento de Ciências Farmacêuticas. Londrina, PR, Brasil. | pt_BR |
Affilliation | Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Patologia. Londrina, PR, Brasil / Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil. | pt_BR |
Affilliation | Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil. | pt_BR |
Affilliation | Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil. | pt_BR |
Affilliation | University of Arizona. Department of Chemistry and Biochemistry. Tucson, Arizona, USA. | En |
Affilliation | Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Patologia. Londrina, PR, Brasil. | pt_BR |
Subject | Nitroxyl | pt_BR |
Subject | Angeli’s salt | pt_BR |
Subject | Nociception | pt_BR |
Subject | Pain | pt_BR |
Subject | Cytokine | pt_BR |
Subject | Nitric oxide | pt_BR |
DeCS | Óxido Nítrico | pt_BR |
DeCS | Nociceptividade | pt_BR |
DeCS | Dor | pt_BR |
DeCS | Citocinas | pt_BR |