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Background: Headache is one of the main painful symptoms described by multiple sclerosis patients. Previously, it was described that neuropathic pain-like behaviors were dependent on transient receptor potential ankyrin 1 (TRPA1) activation in a progressive multiple sclerosis model induced by experimental autoimmune encephalomyelitis (PMS- EAE) in mice. Objective: Here, we aimed to investigate if periorbital mechanical allodynia induced by PMS-EAE was also related to TRPA1 activation. Design and setting: Federal University of Santa Maria, Santa Maria, RS, Brazil. Methods: To induce a PMS-EAE we used female C57BL/6 wild-type and TRPA1- deficient (Trpa1-/-) mice. By the von Frey test, periorbital mechanical allodynia development was observed, and the nociception peak occurred 14 days after induction. At nociception peak day, the mice were treated with sumatriptan, TRPA1 antagonists (HC-030031, A-967079, metamizole, and propyphenazone. Results: The development of mechanical allodynia was showed as well as the antinociceptive effects for all treatments in induced mice. A significant reduction of TRPA1 expression was detected. Conclusion: Thus, these results suggest that headache-like symptoms induced by the PMS-EAE mouse model might occurring by TRPA1 activation.