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Schwann cell TRPA1 elicits reserpine-induced fibromyalgia pain in mice.
Brum, Evelyne Silva; Fialho, Maria Fernanda Pessano; Souza Monteiro de Araújo, Daniel; Landini, Lorenzo; Marini, Matilde; Titiz, Mustafa; Kuhn, Bruna Luiza; Frizzo, Clarissa Piccinin; Araújo, Pedro Henrique Silva; Guimarães, Rafaela Mano; Cunha, Thiago Mattar; Silva, Cássia Regina; Trevisan, Gabriela; Geppetti, Pierangelo; Nassini, Romina; De Logu, Francesco; Oliveira, Sara Marchesan.
Afiliação
  • Brum ES; Graduate Program in Biological Sciences: Toxicological Biochemistry, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, Brazil.
  • Fialho MFP; Graduate Program in Biological Sciences: Toxicological Biochemistry, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, Brazil.
  • Souza Monteiro de Araújo D; Department of Health Sciences, Clinical Pharmacology Unit, University of Florence, Florence, Italy.
  • Landini L; Department of Health Sciences, Clinical Pharmacology Unit, University of Florence, Florence, Italy.
  • Marini M; Department of Health Sciences, Clinical Pharmacology Unit, University of Florence, Florence, Italy.
  • Titiz M; Department of Health Sciences, Clinical Pharmacology Unit, University of Florence, Florence, Italy.
  • Kuhn BL; Heterocycle Chemistry Nucleus (NUQUIMHE), Federal University of Santa Maria, Santa Maria, Brazil.
  • Frizzo CP; Heterocycle Chemistry Nucleus (NUQUIMHE), Federal University of Santa Maria, Santa Maria, Brazil.
  • Araújo PHS; Department of Genetic and Biochemistry, University of Uberlândia, Uberlândia, Brazil.
  • Guimarães RM; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
  • Cunha TM; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
  • Silva CR; Department of Genetic and Biochemistry, University of Uberlândia, Uberlândia, Brazil.
  • Trevisan G; Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, Brazil.
  • Geppetti P; Department of Health Sciences, Clinical Pharmacology Unit, University of Florence, Florence, Italy.
  • Nassini R; Department of Health Sciences, Clinical Pharmacology Unit, University of Florence, Florence, Italy.
  • De Logu F; Department of Health Sciences, Clinical Pharmacology Unit, University of Florence, Florence, Italy.
  • Oliveira SM; Graduate Program in Biological Sciences: Toxicological Biochemistry, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, Brazil.
Br J Pharmacol ; 181(18): 3445-3461, 2024 Sep.
Article em En | MEDLINE | ID: mdl-38772415
ABSTRACT
BACKGROUND AND

PURPOSE:

Fibromyalgia is a complex clinical disorder with an unknown aetiology, characterized by generalized pain and co-morbid symptoms such as anxiety and depression. An imbalance of oxidants and antioxidants is proposed to play a pivotal role in the pathogenesis of fibromyalgia symptoms. However, the precise mechanisms by which oxidative stress contributes to fibromyalgia-induced pain remain unclear. The transient receptor potential ankyrin 1 (TRPA1) channel, known as both a pain sensor and an oxidative stress sensor, has been implicated in various painful conditions. EXPERIMENTAL

APPROACH:

The feed-forward mechanism that implicates reactive oxygen species (ROS) driven by TRPA1 was investigated in a reserpine-induced fibromyalgia model in C57BL/6J mice employing pharmacological interventions and genetic approaches. KEY

RESULTS:

Reserpine-treated mice developed pain-like behaviours (mechanical/cold hypersensitivity) and early anxiety-depressive-like disorders, accompanied by increased levels of oxidative stress markers in the sciatic nerve tissues. These effects were not observed upon pharmacological blockade or global genetic deletion of the TRPA1 channel and macrophage depletion. Furthermore, we demonstrated that selective silencing of TRPA1 in Schwann cells reduced reserpine-induced neuroinflammation (NADPH oxidase 1-dependent ROS generation and macrophage increase in the sciatic nerve) and attenuated fibromyalgia-like behaviours. CONCLUSION AND IMPLICATIONS Activated Schwann cells expressing TRPA1 promote an intracellular pathway culminating in the release of ROS and recruitment of macrophages in the mouse sciatic nerve. These cellular and molecular events sustain mechanical and cold hypersensitivity in the reserpine-evoked fibromyalgia model. Targeting TRPA1 channels on Schwann cells could offer a novel therapeutic approach for managing fibromyalgia-related behaviours.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Reserpina / Células de Schwann / Fibromialgia / Espécies Reativas de Oxigênio / Estresse Oxidativo / Canal de Cátion TRPA1 / Camundongos Endogâmicos C57BL Limite: Animals Idioma: En Revista: Br J Pharmacol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Reserpina / Células de Schwann / Fibromialgia / Espécies Reativas de Oxigênio / Estresse Oxidativo / Canal de Cátion TRPA1 / Camundongos Endogâmicos C57BL Limite: Animals Idioma: En Revista: Br J Pharmacol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido