Characterisation of periorbital mechanical allodynia in the reserpine-induced fibromyalgia model in mice: The role of the Schwann cell TRPA1/NOX1 signalling pathway
Abstract
Fibromyalgia (FM) is a complex and multifaceted condition characterized by a range of clinical symptoms, including widespread pain and a strong association with migraine headaches. Recent findings have underscored the role of oxidative stress and transient receptor potential ankyrin 1 (TRPA1) channel in migraine and FM. However, the precise mechanisms underlying the comorbidity between migraine and FM are unclear. Periorbital mechanical allodynia (PMA), which recapitulates one of the major symptoms of migraine, and the feed-forward mechanism driven by reactive oxygen species and TRPA1, were investigated in a reserpine-induced FM model in C57BL/6J mice, employing pharmacological interventions and genetic approaches. Reserpine-treated mice developed PMA (which was alleviated by antimigraine drugs) and increased endoneurial macrophages and oxidative stress markers in the trigeminal nerve tissues (neuroinflammation). These responses were absent upon macrophage depletion and by pharmacological inhibition or global genetic deletion of the TRPA1 channel. Furthermore, selective silencing of TRPA1 in Schwann cells attenuated both reserpine-induced PMA and neuroinflammation, while selective silencing of TRPA1 in sensory neurons reduced PMA but not neuroinflammation. In reserpine-treated mice, Schwann cell TRPA1 promoted NADPH oxidase 1-mediated reactive oxygen species generation and macrophage density increase in the mouse trigeminal nerve, which sustains PMA. Targeting TRPA1 channels in Schwann cells could offer a novel therapeutic strategy for FM-related headaches.
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Macrophage infiltration in trigeminal nerve tissues in fibromyalgia model mice suggests that monocytes/macrophages are closely related to neuropathic pain.
“Recent studies have reported macrophage infiltration in the trigeminal nerve tissues in FMS model mice, suggesting that monocytes/macrophages are closely related to NP (55).”
From Nociplastic pain: the prominent role of non-neuronal cells in central and peripheral sensitization (2026) · cites this paper as [55]
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Self-citationBrum, E. D. S., Fialho, M. F. P., de Araújo, D. S. M., Landini, L., Marini, M., Logu, F. D., Nassini, R., & Oliveira, S. M. (2026) · Journal of Neurochemistry · doi:10.1111/jnc.70424 · Cited by 2 · see citing works
Self-citationA delayed endothelial–glial mechanism for CGRP-induced migraine
Lennerz, J. K., & Meßlinger, K. (2026) · The Journal of Headache and Pain · doi:10.1186/s10194-026-02455-3
Antoniazzi, C. T. D. D., Brito, H. A., Rodrigues, P., Fim, Y. V., Ruviaro, N. A., Machado, A. C., & Trevisan, G. (2026) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2026.179210
Torres, I. L. S., Paludo, R. H., Laste, G., Fidélis, M. E. S., Moreira, E. R. A. D. S., Steimetz, L. C., Fregni, F., Caumo, W., & Stein, D. J. (2026) · Biomedicines · doi:10.20944/preprints202609.2412.v1
Marini, M., Chieca, M., Coppi, E., Montini, M., Bonacchi, L., Landini, L., Scuffi, I., Kwan, K. Y., Papini, A., Siena, G. D., et al. (2026) · Journal of Clinical Investigation · doi:10.1172/jci206667
Self-citationAlkaloid fraction of Psychotria nemorosa reduces fibromyalgia-like symptoms in mice
Lise, P. D. C. D., Zilli, G. A. L., Cardoso, H., Bertoncello, K. T., Becker, G., Atuati, S. F., Scussel, R., Apolidório, N. S., Gasparetto, R. L., Oliveira, S. M., et al. (2026) · Inflammopharmacology · doi:10.1007/s10787-026-02431-y
Self-citation
- Authors
- Brum, E. S., Landini, L., Souza Monteiro de Araújo, D., Marini, M., Geppetti, P., Nassini, R., De Logu, F., & Oliveira, S. M.
- Affiliations
- University of Florence (IT)
- Universidade Federal de Santa Maria (BR)
- Corresponding author
- Nassini, Romina
- ORCID
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2025-03
- Volume
- 229
- Pages
- 289-299
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W4406606592
- Cited by
- 8
- References
- 76
- Citations by year
- 2026: 6 · 2025: 2
- FWCI
- 5.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion)
- Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (150611/2022-6, 309404/2023-1, 88887.475201/2020-00, 88887.185973/2018-00)
- Telethon Foundation
- NextGenerationEU
- European Research Council (835286)
- Horizon 2020
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Coordination of Higher Education Personnel Improvement (88881.844988/2023-01)
- European Union
- Government of Italy Ministry of Education University and Research
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Migraine and Headache Studies
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- fibromyalgia, migraine, TRPA1, Schwann cells, NOX1, reactive oxygen species, oxidative stress, neuroinflammation, trigeminal nerve, sensory neurons
- MeSH terms
- TRPA1 Cation Channel, NADPH Oxidase 1, Animals, Disease Models, Animal, Fibromyalgia, Humans, Hyperalgesia, Macrophages, Male, Mice, Inbred C57BL, Migraine Disorders, Reserpine, Schwann Cells, Trigeminal Nerve, Signal Transduction, Reactive Oxygen Species, Mice, Knockout, Oxidative Stress, Mice
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