Schwann cell TRPA1 elicits reserpine‐induced fibromyalgia pain in mice
Fuente:
Wiley Open Access
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Artículo Open Access |
| Published: |
Wiley
2024
|
| Subjects: | |
| Online Access: | |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1867012815681748992 |
|---|---|
| author | Evelyne Silva Brum Maria Fernanda Pessano Fialho Daniel Souza Monteiro de Araújo Lorenzo Landini Matilde Marini Mustafa Titiz Bruna Luiza Kuhn Clarissa Piccinin Frizzo Pedro Henrique Silva Araújo Rafaela Mano Guimarães Thiago Mattar Cunha Cássia Regina Silva Gabriela Trevisan Pierangelo Geppetti Romina Nassini Francesco De Logu Sara Marchesan Oliveira |
| author_facet | Evelyne Silva Brum Maria Fernanda Pessano Fialho Daniel Souza Monteiro de Araújo Lorenzo Landini Matilde Marini Mustafa Titiz Bruna Luiza Kuhn Clarissa Piccinin Frizzo Pedro Henrique Silva Araújo Rafaela Mano Guimarães Thiago Mattar Cunha Cássia Regina Silva Gabriela Trevisan Pierangelo Geppetti Romina Nassini Francesco De Logu Sara Marchesan Oliveira Evelyne Silva Brum Maria Fernanda Pessano Fialho Daniel Souza Monteiro de Araújo Lorenzo Landini Matilde Marini Mustafa Titiz Bruna Luiza Kuhn Clarissa Piccinin Frizzo Pedro Henrique Silva Araújo Rafaela Mano Guimarães Thiago Mattar Cunha Cássia Regina Silva Gabriela Trevisan Pierangelo Geppetti Romina Nassini Francesco De Logu Sara Marchesan Oliveira |
| collection | Wiley Open Access |
| contents | Schwann cell TRPA1 elicits reserpine‐induced fibromyalgia pain in mice Evelyne Silva Brum Maria Fernanda Pessano Fialho Daniel Souza Monteiro de Araújo Lorenzo Landini Matilde Marini Mustafa Titiz Bruna Luiza Kuhn Clarissa Piccinin Frizzo Pedro Henrique Silva Araújo Rafaela Mano Guimarães Thiago Mattar Cunha Cássia Regina Silva Gabriela Trevisan Pierangelo Geppetti Romina Nassini Francesco De Logu Sara Marchesan Oliveira British Journal of Pharmacology Background and PurposeFibromyalgia 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 ApproachThe 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 ResultsReserpine‐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 ImplicationsActivated 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. 10.1111/bph.16413 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1111/bph.16413 |
| format | Artículo Open Access |
| id | wiley_oa_10_1111_bph_16413 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2024 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Schwann cell TRPA1 elicits reserpine‐induced fibromyalgia pain in mice Evelyne Silva Brum Maria Fernanda Pessano Fialho Daniel Souza Monteiro de Araújo Lorenzo Landini Matilde Marini Mustafa Titiz Bruna Luiza Kuhn Clarissa Piccinin Frizzo Pedro Henrique Silva Araújo Rafaela Mano Guimarães Thiago Mattar Cunha Cássia Regina Silva Gabriela Trevisan Pierangelo Geppetti Romina Nassini Francesco De Logu Sara Marchesan Oliveira British Journal of Pharmacology Schwann cell TRPA1 elicits reserpine‐induced fibromyalgia pain in mice Evelyne Silva Brum Maria Fernanda Pessano Fialho Daniel Souza Monteiro de Araújo Lorenzo Landini Matilde Marini Mustafa Titiz Bruna Luiza Kuhn Clarissa Piccinin Frizzo Pedro Henrique Silva Araújo Rafaela Mano Guimarães Thiago Mattar Cunha Cássia Regina Silva Gabriela Trevisan Pierangelo Geppetti Romina Nassini Francesco De Logu Sara Marchesan Oliveira British Journal of Pharmacology Background and PurposeFibromyalgia 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 ApproachThe 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 ResultsReserpine‐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 ImplicationsActivated 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. 10.1111/bph.16413 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | Schwann cell TRPA1 elicits reserpine‐induced fibromyalgia pain in mice |
| topic | British Journal of Pharmacology |
| url | https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.16413 |