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dc.contributor.authorLonghi-Balbinot, Daniela T
dc.contributor.authorRossaneis, Ana C
dc.contributor.authorPinho-Ribeiro, Felipe A
dc.contributor.authorBertozzi, Mariana M
dc.contributor.authorCunha, Fernando Q
dc.contributor.authorAlves-Filho, José C
dc.contributor.authorCunha, Thiago M
dc.contributor.authorPeron, Jean P S
dc.contributor.authorMiranda, Katrina M
dc.contributor.authorCasagrande, Rubia
dc.contributor.authorVerri, Waldiceu A
dc.date.accessioned2016-12-07T01:47:03Z
dc.date.available2016-12-07T01:47:03Z
dc.date.issued2016-08-25
dc.identifier.citationThe nitroxyl donor, Angeli's salt, reduces chronic constriction injury-induced neuropathic pain. 2016, 256:1-8 Chem. Biol. Interact.en
dc.identifier.issn1872-7786
dc.identifier.pmid27287419
dc.identifier.doi10.1016/j.cbi.2016.06.009
dc.identifier.urihttp://hdl.handle.net/10150/621523
dc.description.abstractChronic pain is a major health problem worldwide. We have recently demonstrated the analgesic effect of the nitroxyl donor, Angeli's salt (AS) in models of inflammatory pain. In the present study, the acute and chronic analgesic effects of AS was investigated in chronic constriction injury of the sciatic nerve (CCI)-induced neuropathic pain in mice. Acute (7th day after CCI) AS treatment (1 and 3 mg/kg; s.c.) reduced CCI-induced mechanical, but not thermal hyperalgesia. The acute analgesic effect of AS was prevented by treatment with 1H-[1,2, 4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, a soluble guanylate cyclase inhibitor), KT5823 (an inhibitor of protein kinase G [PKG]) or glibenclamide (GLB, an ATP-sensitive potassium channel blocker). Chronic (7-14 days after CCI) treatment with AS (3 mg/kg, s.c.) promoted a sustained reduction of CCI-induced mechanical and thermal hyperalgesia. Acute AS treatment reduced CCI-induced spinal cord allograft inflammatory factor 1 (known as Iba-1), interleukin-1β (IL-1β), and ST2 receptor mRNA expression. Chronic AS treatment reduced CCI-induced spinal cord glial fibrillary acidic protein (GFAP), Iba-1, IL-1β, tumor necrosis factor-α (TNF-α), interleukin-33 (IL-33) and ST2 mRNA expression. Chronic treatment with AS (3 mg/kg, s.c.) did not alter aspartate aminotransferase, alanine aminotransferase, urea or creatinine plasma levels. Together, these results suggest that the acute analgesic effect of AS depends on activating the cGMP/PKG/ATP-sensitive potassium channel signaling pathway. Moreover, chronic AS diminishes CCI-induced mechanical and thermal hyperalgesia by reducing the activation of spinal cord microglia and astrocytes, decreasing TNF-α, IL-1β and IL-33 cytokines expression. This spinal cord immune modulation was more prominent in the chronic treatment with AS. Thus, nitroxyl limits CCI-induced neuropathic pain by reducing spinal cord glial cells activation.
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Brazil); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, Brazil); Coordenadoria de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, Brazil); Ministerio da Ciencia, Tecnologia e Inovacao (MCTI, Brazil); Secretaria da Ciencia, Tecnologia e Ensino Superior (SETI, Brazil)/Fundacao Araucaria (Brazil); Parana State Goverment (Brazil); CAPES/Fundacao Araucaria; CAPES; National Institutes of Health [R01-GM076247]en
dc.language.isoenen
dc.publisherELSEVIER IRELAND LTDen
dc.relation.urlhttp://www.sciencedirect.com/science/article/pii/S0009279716302253en
dc.rights© 2016 Elsevier Ireland Ltd. All rights reserveden
dc.subjectNitroxyl donoren
dc.subjectNeuropathic painen
dc.subjectAstrocytesen
dc.subjectMicrogliaen
dc.subjectCytokinesen
dc.titleThe nitroxyl donor, Angeli's salt, reduces chronic constriction injury-induced neuropathic pain.en
dc.typeArticleen
dc.contributor.departmentUniv Arizona, Dept Chem & Biochemen
dc.identifier.journalChemico-biological interactionsen
dc.description.noteAvailable online 7 June 2016; 12 month embargo.en
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en
dc.eprint.versionFinal accepted manuscripten
refterms.dateFOA2017-06-07T00:00:00Z
html.description.abstractChronic pain is a major health problem worldwide. We have recently demonstrated the analgesic effect of the nitroxyl donor, Angeli's salt (AS) in models of inflammatory pain. In the present study, the acute and chronic analgesic effects of AS was investigated in chronic constriction injury of the sciatic nerve (CCI)-induced neuropathic pain in mice. Acute (7th day after CCI) AS treatment (1 and 3 mg/kg; s.c.) reduced CCI-induced mechanical, but not thermal hyperalgesia. The acute analgesic effect of AS was prevented by treatment with 1H-[1,2, 4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, a soluble guanylate cyclase inhibitor), KT5823 (an inhibitor of protein kinase G [PKG]) or glibenclamide (GLB, an ATP-sensitive potassium channel blocker). Chronic (7-14 days after CCI) treatment with AS (3 mg/kg, s.c.) promoted a sustained reduction of CCI-induced mechanical and thermal hyperalgesia. Acute AS treatment reduced CCI-induced spinal cord allograft inflammatory factor 1 (known as Iba-1), interleukin-1β (IL-1β), and ST2 receptor mRNA expression. Chronic AS treatment reduced CCI-induced spinal cord glial fibrillary acidic protein (GFAP), Iba-1, IL-1β, tumor necrosis factor-α (TNF-α), interleukin-33 (IL-33) and ST2 mRNA expression. Chronic treatment with AS (3 mg/kg, s.c.) did not alter aspartate aminotransferase, alanine aminotransferase, urea or creatinine plasma levels. Together, these results suggest that the acute analgesic effect of AS depends on activating the cGMP/PKG/ATP-sensitive potassium channel signaling pathway. Moreover, chronic AS diminishes CCI-induced mechanical and thermal hyperalgesia by reducing the activation of spinal cord microglia and astrocytes, decreasing TNF-α, IL-1β and IL-33 cytokines expression. This spinal cord immune modulation was more prominent in the chronic treatment with AS. Thus, nitroxyl limits CCI-induced neuropathic pain by reducing spinal cord glial cells activation.


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