Periorbital Nociception in a Progressive Multiple Sclerosis Mouse Model Is Dependent on TRPA1 Channel Activation

Autor:	Camila Duarte Ritter, Juliano Ferreira, Francesco De Logu, Gabriela Trevisan, Romina Nassini, Lorenzo Landini, Diéssica Padilha Dalenogare, Sara Marchesan Oliveira, Caren Tatiane de David Antoniazzi, Maria Fernanda Pessano Fialho, Guilherme Vargas Bochi, Débora Denardin Lückemeyer, Fernando Bellinaso, Pierangelo Geppetti, Sabrina Qader Kudsi, Gabriele Cheiran Pereira
Jazyk:	angličtina
Rok vydání:	2021
Předmět:	Pharmaceutical Science Pharmacology Calcitonin gene-related peptide Olcegepant calcitonin gene-related peptide Article chemistry.chemical_compound Trigeminal ganglion Pharmacy and materia medica Drug Discovery medicine migraine metamizole NADPH oxidase biology business.industry Experimental autoimmune encephalomyelitis food and beverages medicine.disease sumatriptan RS1-441 Nociception chemistry Apocynin biology.protein Nociceptor Molecular Medicine Medicine anti-oxidants business headache psychological phenomena and processes
Zdroj:	Pharmaceuticals Pharmaceuticals, Vol 14, Iss 831, p 831 (2021) Volume 14 Issue 8 Pharmaceuticals (Basel)
ISSN:	1424-8247
Popis:	Headaches are frequently described in progressive multiple sclerosis (PMS) patients, but their mechanism remains unknown. Transient receptor potential ankyrin 1 (TRPA1) was involved in neuropathic nociception in a model of PMS induced by experimental autoimmune encephalomyelitis (PMS-EAE), and TRPA1 activation causes periorbital and facial nociception. Thus, our purpose was to observe the development of periorbital mechanical allodynia (PMA) in a PMS-EAE model and evaluate the role of TRPA1 in periorbital nociception. Female PMS-EAE mice elicited PMA from day 7 to 14 days after induction. The antimigraine agents olcegepant and sumatriptan were able to reduce PMA. The PMA was diminished by the TRPA1 antagonists HC-030031, A-967079, metamizole and propyphenazone and was absent in TRPA1-deficient mice. Enhanced levels of TRPA1 endogenous agonists and NADPH oxidase activity were detected in the trigeminal ganglion of PMS-EAE mice. The administration of the anti-oxidants apocynin (an NADPH oxidase inhibitor) or alpha-lipoic acid (a sequestrant of reactive oxygen species), resulted in PMA reduction. These results suggest that generation of TRPA1 endogenous agonists in the PMS-EAE mouse model may sensitise TRPA1 in trigeminal nociceptors to elicit PMA. Thus, this ion channel could be a potential therapeutic target for the treatment of headache in PMS patients.
Databáze:	OpenAIRE
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