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Experimental Trypanosoma cruzi Infection Induces Pain in Mice Dependent on Early Spinal Cord Glial Cells and NFκB Activation and Cytokine Production.
Borghi, Sergio M; Fattori, Victor; Carvalho, Thacyana T; Tatakihara, Vera L H; Zaninelli, Tiago H; Pinho-Ribeiro, Felipe A; Ferraz, Camila R; Staurengo-Ferrari, Larissa; Casagrande, Rubia; Pavanelli, Wander R; Cunha, Fernando Q; Cunha, Thiago M; Pinge-Filho, Phileno; Verri, Waldiceu A.
Afiliação
  • Borghi SM; Department of Pathology, Center of Biological Science, State University of Londrina, Londrina, Brazil.
  • Fattori V; Center for Research in Health Science, University of Northern Paraná-Unopar, Londrina, Brazil.
  • Carvalho TT; Department of Pathology, Center of Biological Science, State University of Londrina, Londrina, Brazil.
  • Tatakihara VLH; Department of Pathology, Center of Biological Science, State University of Londrina, Londrina, Brazil.
  • Zaninelli TH; Department of Pathology, Center of Biological Science, State University of Londrina, Londrina, Brazil.
  • Pinho-Ribeiro FA; Department of Pathology, Center of Biological Science, State University of Londrina, Londrina, Brazil.
  • Ferraz CR; Department of Pathology, Center of Biological Science, State University of Londrina, Londrina, Brazil.
  • Staurengo-Ferrari L; Department of Pathology, Center of Biological Science, State University of Londrina, Londrina, Brazil.
  • Casagrande R; Department of Pathology, Center of Biological Science, State University of Londrina, Londrina, Brazil.
  • Pavanelli WR; Departament of Pharmaceutical Sciences, Health Sciences Center, University Hospital, Londrina State University, Londrina, Brazil.
  • Cunha FQ; Department of Pathology, Center of Biological Science, State University of Londrina, Londrina, Brazil.
  • Cunha TM; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
  • Pinge-Filho P; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
  • Verri WA; Department of Pathology, Center of Biological Science, State University of Londrina, Londrina, Brazil.
Front Immunol ; 11: 539086, 2020.
Article em En | MEDLINE | ID: mdl-33574810
The neglected tropical infirmity Chagas disease (CD) presents high mortality. Its etiological agent T. cruzi is transmitted by infected hematophagous insects. Symptoms of the acute phase of the infection include fever, fatigue, body aches, and headache, making diagnosis difficult as they are present in other illnesses as well. Thus, in endemic areas, individuals with undetermined pain may be considered for CD. Although pain is a characteristic symptom of CD, its cellular and molecular mechanisms are unknown except for demonstration of a role for peripheral TNF-α in CD pain. In this study, we evaluate the role of spinal cord glial cells in experimental T. cruzi infection in the context of pain using C57BL/6 mice. Pain, parasitemia, survival, and glial and neuronal function as well as NFκB activation and cytokine/chemokine production were assessed. T. cruzi infection induced chronic mechanical and thermal hyperalgesia. Systemic TNF-α and IL-1ß peaked 14 days postinfection (p.i.). Infected mice presented increased spinal gliosis and NFκB activation compared to uninfected mice at 7 days p.i. Glial and NFκB inhibitors limited T. cruzi-induced pain. Nuclear phosphorylated NFκB was detected surrounded by glia markers, and glial inhibitors reduced its detection. T. cruzi-induced spinal cord production of cytokines/chemokines was also diminished by glial inhibitors. Dorsal root ganglia (DRG) neurons presented increased activity in infected mice, and the production of inflammatory mediators was counteracted by glial/NFκB inhibitors. The present study unveils the contribution of DRG and spinal cord cellular and molecular events leading to pain in T. cruzi infection, contributing to a better understanding of CD pathology.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dor / Medula Espinal / Trypanosoma cruzi / Neuroglia / Citocinas / NF-kappa B / Doença de Chagas Limite: Animals Idioma: En Revista: Front Immunol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dor / Medula Espinal / Trypanosoma cruzi / Neuroglia / Citocinas / NF-kappa B / Doença de Chagas Limite: Animals Idioma: En Revista: Front Immunol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça