Repeated TRPA1 Blockade Reduces Nociception and Neuroinflammation in a Relapsing–Remitting Mouse Model of Multiple Sclerosis
4 affiliations
- 1Graduate Program in Pharmacology, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, Brazil
- 2The Alan Edwards Centre for Research on Pain, Lyman Duff Medical Building, McGill University, Montréal, QC H3A 2B4, Canada
- 3Graduate Program in Veterinary Medicine, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, Brazil
- 4Graduate Program in Biological Sciences, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, Brazil
Abstract
Relapsing–remitting multiple sclerosis (RRMS) is a chronic autoimmune and neurodegenerative disease characterized by neuroinflammation and demyelination. Neuropathic pain is a frequent and poorly managed symptom associated with oxidative stress. Transient receptor potential ankyrin 1 (TRPA1), which is activated by oxidative mediators, contributes to nociceptive signaling and neuroinflammatory processes in the relapsing–remitting experimental autoimmune encephalomyelitis (RR-EAE) model. This study investigated the effects of repeated pharmacological blockade of TRPA1 on nociceptive behaviors and disease-associated pathological mechanisms using an RR-EAE mouse model. Female C57BL/6 mice received the TRPA1 antagonist A-967079 (30 mg/kg, intragastric) from day 16 to day 36 post-induction. Behavioral, molecular, and biochemical analyses were performed. Repeated administration of A-967079 attenuated mechanical and cold allodynia without impairing locomotor function or altering body weight. TRPA1 antagonism modulated glial marker expression and plasma pro-inflammatory cytokine levels. A-967079 attenuated oxidative stress, reducing hydrogen peroxide, 4-hydroxynonenal, advanced oxidation protein product levels (TRPA1 endogenous agonists), and NADPH–cytochrome c reductase activity. These findings demonstrate that repeated TRPA1 antagonism effectively modulates neuropathic pain-like behaviors and targets key pathological mechanisms associated with RRMS. This approach closely reflects clinical management, as treatment was initiated after disease onset, when symptoms were already present. Our results support TRPA1 antagonism as a promising therapeutic strategy for pain management in RRMS.
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BibTeX
@article{luiz2026repeated,
title = {{Repeated TRPA1 Blockade Reduces Nociception and Neuroinflammation in a Relapsing–Remitting Mouse Model of Multiple Sclerosis}},
author = {Ana Clara Machado Luiz and Diulle Spat Peres and Sabrina Qader Kudsi and Ricardo Iuri Felix Moraes and Caren Antoniazzi and Leonardo Gomes Pereira and Helen Alves Brito and Micheli Mainardi Pillat and Mariana Martins Flores and Patrícia Rodrigues and Gabriela Trevisan},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219592},
url = {https://www.mdpi.com/1422-0067/27/21/9592},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Repeated TRPA1 Blockade Reduces Nociception and Neuroinflammation in a Relapsing–Remitting Mouse Model of Multiple Sclerosis
AU - Ana Clara Machado Luiz
AU - Diulle Spat Peres
AU - Sabrina Qader Kudsi
AU - Ricardo Iuri Felix Moraes
AU - Caren Antoniazzi
AU - Leonardo Gomes Pereira
AU - Helen Alves Brito
AU - Micheli Mainardi Pillat
AU - Mariana Martins Flores
AU - Patrícia Rodrigues
AU - Gabriela Trevisan
PY - 2026
DA - 2026/10/27
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219592
UR - https://www.mdpi.com/1422-0067/27/21/9592
AB - Relapsing–remitting multiple sclerosis (RRMS) is a chronic autoimmune and neurodegenerative disease characterized by neuroinflammation and demyelination. Neuropathic pain is a frequent and poorly managed symptom associated with oxidative stress. Transient receptor potential ankyrin 1 (TRPA1), which is activated by oxidative mediators, contributes to nociceptive signaling and neuroinflammatory processes in the relapsing–remitting experimental autoimmune encephalomyelitis (RR-EAE) model. This study investigated the effects of repeated pharmacological blockade of TRPA1 on nociceptive behaviors and disease-associated pathological mechanisms using an RR-EAE mouse model. Female C57BL/6 mice received the TRPA1 antagonist A-967079 (30 mg/kg, intragastric) from day 16 to day 36 post-induction. Behavioral, molecular, and biochemical analyses were performed. Repeated administration of A-967079 attenuated mechanical and cold allodynia without impairing locomotor function or altering body weight. TRPA1 antagonism modulated glial marker expression and plasma pro-inflammatory cytokine levels. A-967079 attenuated oxidative stress, reducing hydrogen peroxide, 4-hydroxynonenal, advanced oxidation protein product levels (TRPA1 endogenous agonists), and NADPH–cytochrome c reductase activity. These findings demonstrate that repeated TRPA1 antagonism effectively modulates neuropathic pain-like behaviors and targets key pathological mechanisms associated with RRMS. This approach closely reflects clinical management, as treatment was initiated after disease onset, when symptoms were already present. Our results support TRPA1 antagonism as a promising therapeutic strategy for pain management in RRMS.
SN - 1422-0067
ER -