• Diéssica P Dalenogare, Maria C Theisen, Diulle S Peres, Maria F P Fialho, Nathaly Andrighetto, Laura Barros, Lorenzo Landini, Mustafa Titiz, Francesco De Logu, Sara M Oliveira, Pierangelo Geppetti, Romina Nassini, and Gabriela Trevisan.
• Department of Physiology and Pharmacology, Graduate Program in Pharmacology, Federal University of Santa Maria (UFSM), Avenida Roraima, Santa Maria, RS, Brazil.
• Pain. 2022 Jul 1; 163 (7): 134613551346-1355.

AbstractPrimary headache conditions are frequently associated with multiple sclerosis (MS), but the mechanism that triggers or worsens headaches in patients with MS is poorly understood. We previously showed that the proalgesic transient receptor potential ankyrin 1 (TRPA1) mediates hind paw mechanical and cold allodynia in a relapsing-remitting experimental autoimmune encephalomyelitis (RR-EAE) model in mice. Here, we investigated the development of periorbital mechanical allodynia (PMA) in RR-EAE, a hallmark of headache, and if TRPA1 contributed to this response. RR-EAE induction by injection of the myelin oligodendrocyte peptide fragment35-55 (MOG35-55) and Quillaja A adjuvant (Quil A) in C57BL/6J female mice elicited a delayed and sustained PMA. The PMA at day 35 after induction was reduced by the calcitonin gene-related peptide receptor antagonist (olcegepant) and the serotonin 5-HT1B/D receptor agonist (sumatriptan), 2 known antimigraine agents. Genetic deletion or pharmacological blockade of TRPA1 attenuated PMA associated with RR-EAE. The levels of oxidative stress biomarkers (4-hydroxynonenal and hydrogen peroxide, known TRPA1 endogenous agonists) and superoxide dismutase and NADPH oxidase activities were increased in the trigeminal ganglion of RR-EAE mice. Besides, the treatment with antioxidants (apocynin or α-lipoic acid) attenuated PMA. Thus, the results of this study indicate that TRPA1, presumably activated by endogenous agonists, evokes PMA in a mouse model of relapsing-remitting MS.Copyright © 2021 International Association for the Study of Pain.

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