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Effects of selective inhibition of nNOS and iNOS on neuropathic pain in rats

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Autor(es):
Rocha, P. A. [1] ; Ferreira, A. F. B. [2] ; Da Silva, J. T. [3, 4] ; Alves, A. S. [2] ; Martins, D. O. [1, 5] ; Britto, L. R. G. [2] ; Chacur, M. [1, 5]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Dept Anat, Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Dept Physiol & Biophys, Sao Paulo, SP - Brazil
[3] Univ Maryland Baltimore, Dept Neural & Pain Sci, Baltimore, MD - USA
[4] Johns Hopkins Univ, Dept Psychiat, Baltimore, MD 21218 - USA
[5] Da Silva, J. T., Johns Hopkins Univ, Dept Psychiat, Baltimore, MD 21218 USA.Rocha, P. A., Univ Sao Paulo, Dept Anat, Sao Paulo, SP - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: Molecular and Cellular Neuroscience; v. 105, JUN 2020.
Citações Web of Science: 0
Resumo

Various animal models have been employed to understand the pathogenic mechanism of neuropathic pain. Nitric oxide (NO) is an important molecule in nociceptive transmission and is involved in neuropathic pain. However, its mechanistic actions remain unclear. The aim of this study was to better understand the involvement of neuronal and inducible isoforms of nitric oxide synthase (nNOS and iNOS) in neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve in rats. We evaluated pain sensitivity (mechanical with-drawal thresholds using Randall and Selitto, and von Frey tests, and thermal withdrawal thresholds using Hargreaves test) prior to CCI surgery, 14 days post CCI and after intrathecal injections of selective nNOS or iNOS inhibitors. We also evaluated the distribution of NOS isozymes in the spinal cord and dorsal root ganglia (DRG) by immunohistochemistry, synthesis of iNOS and nNOS by Western blot, and NO production using fluorescent probe DAF-2 DA (DA). Our results showed higher number of nNOS and iNOS-positive neurons in the spinal cord and DRG of CCI compared to sham rats, and their reduction in CCI rats after treatment with selective inhibitors compared to non-treated groups. Western blot results also indicated reduced expression of nNOS and iNOS after treatment with selective inhibitors. Furthermore, both inhibitors reduced CCI-evoked mechanical and thermal withdrawal thresholds but only nNOS inhibitor was able to efficiently lower mechanical withdrawal thresholds using von Frey test. In addition, we observed higher NO production in the spinal cord and DRG of injured rats compared to control group. Our study innovatively shows that nNOS may strongly modulate nociceptive transmission in rats with neuropathic pain, while iNOS may partially participate in the development of nociceptive responses. Thus, drugs targeting nNOS for neuropathic pain may represent a potential therapeutic strategy. (AU)

Processo FAPESP: 11/22268-0 - Aplicação do laser no controle da dor e na estimulação tecidual: da pesquisa básica à aplicação clínica
Beneficiário:Marucia Chacur
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 17/05218-5 - Efeito da fotobioestimulação em diferentes neuropatias periférica em ratos.
Beneficiário:Marucia Chacur
Linha de fomento: Auxílio à Pesquisa - Regular