The nitroxyl donor, Angeli’s salt, inhibits inflammatory hyperalgesia in rats

dc.creatorZarpelon, Ana Carla
dc.creatorSouza, Guilherme R.
dc.creatorCunha, Thiago M.
dc.creatorSchivo, Ieda R.S.
dc.creatorMarchesi, Mario
dc.creatorCasagrande, Rubia
dc.creatorPinge-Filho, Phileno
dc.creatorCunha, Fernando Q.
dc.creatorFerreira, Sergio H.
dc.creatorMiranda, Katrina M.
dc.creatorVerri Jr, Waldiceu Aparecido
dc.date2016-09-30T19:38:48Z
dc.date2016-09-30T19:38:48Z
dc.date2013
dc.date.accessioned2023-09-26T20:29:27Z
dc.date.available2023-09-26T20:29:27Z
dc.identifierZARPELON, Ana Carla et al. The nitroxyl donor, Angeli’s salt, inhibits inflammatory hyperalgesia in rats. Neuropharmacology, n. 71, p. 1-9, 2013.
dc.identifier0028-3908
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/16029
dc.identifier10.1016/j.neuropharm.2013.03.009
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8858059
dc.descriptionCNPq (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
dc.descriptionNitric 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherBruno Frenguelli
dc.rightsopen access
dc.subjectNitroxyl
dc.subjectAngeli’s salt
dc.subjectNociception
dc.subjectPain
dc.subjectCytokine
dc.subjectNitric oxide
dc.subjectÓxido Nítrico
dc.subjectNociceptividade
dc.subjectDor
dc.subjectCitocinas
dc.titleThe nitroxyl donor, Angeli’s salt, inhibits inflammatory hyperalgesia in rats
dc.typeArticle


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