Repeated TRPA1 Blockade Reduces Nociception and Neuroinflammation in a Relapsing–Remitting Mouse Model of Multiple Sclerosis

Authors:
Open Access
Publisher website
Google Scholar
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.
Funding Information
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (#303485/2026-4)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (402536/2024-0)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (#173401/2023-6)
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (#88887.002501/2024-00)

This publication has 50 references indexed in Scilit: