| Autor: |
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 |
| Předmět: |
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| Zdroj: |
British Journal of Pharmacology; Sep2024, Vol. 181 Issue 18, p3445-3461, 17p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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