Participação do receptor TRPA1 na nocicepção observada em um modelo de esclerose múltipla progressiva em camundongos

• Ano de defesa: 2020
• Autor(a) principal: Ritter, Camila dos Santos
• Orientador(a): Santos, Gabriela Trevisan dos
• Banca de defesa: André, Eunice, Oliveira, Mauro Schneider
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Santa Maria; Centro de Ciências da Saúde
• Programa de Pós-Graduação: Programa de Pós-Graduação em Farmacologia
• Departamento: Farmacologia
• País: Brasil
• Palavras-chave em Português: Dor neuropática central; 4-HNE; NADPH oxidase; EAE; Apocinina; Ácido α-lipóico
• Palavras-chave em Inglês: Central neuropathic pain; Apocynin; α-lipoic acid
• Área do conhecimento CNPq: CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
• Link de acesso: http://repositorio.ufsm.br/handle/1/24007

Central neuropathic pain (CNP) is a common untreated symptom in progressive multiple sclerosis (PMS) and is associated with poor quality of life and interference with patients’ daily activities. The neuroinflammation process and mitochondrial dysfunction in the PPMS lesions generate reactive species. The transient potential receptor ankyrin 1 (TRPA1) has been identified as one of the major mechanisms that contribute to neuropathic pain signaling and can be activated by products of oxidative stress. Thus, the goal of our study was to evaluate the role of spinal cord TRPA1 in a PPMS mice model. C57BL/6 female mice (20-30g) were used and the PMS model was induced by the experimental autoimmune encephalomyelitis (EAE) using MOG35-55 antigen and CFA (complete Freund’s adjuvant). Mice developed progressive clinical score, with motor impairment observed after 15 days of induction. This model induced progressive mechanical and cold allodynia, and heat hyperalgesia which were measured up to 14 days after induction. The hypersensitivity observed was reduced by the administration of selective TRPA1 antagonists (HC-030031 and A967079, via intrathecal and intragastric), antioxidants (α-lipoic acid and apocynin, via intrathecal and intragastric), and TRPA1 antisense oligonucleotide (via intrathecal). We also observed an increase in TRPA1 mRNA levels, NADPH oxidase activity, and 4-hydroxinonenal (a TRPA1 agonist) levels in spinal cord sample of PMS-induced animals. In conclusion, these results support the hypothesis of the TRPA1 receptor involvement in nociception observed in a PMS model in mice.