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Article

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

1
Graduated Program in Pharmacology, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, RS, Brazil
2
Graduated Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, RS, Brazil
3
Graduated Program in Pharmacology, Federal University of Santa Catarina (UFSC), Florianópolis 88040-900, SC, Brazil
4
Department of Health Science, Clinical Pharmacology and Oncology, University of Florence, 50139 Florence, FI, Italy
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Arpad Szallasi
Pharmaceuticals 2021, 14(8), 831; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14080831
Received: 13 July 2021 / Revised: 16 August 2021 / Accepted: 17 August 2021 / Published: 23 August 2021
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. View Full-Text
Keywords: metamizole; anti-oxidants; calcitonin gene-related peptide; sumatriptan; migraine; headache metamizole; anti-oxidants; calcitonin gene-related peptide; sumatriptan; migraine; headache
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MDPI and ACS Style

Dalenogare, D.P.; Ritter, C.; Bellinaso, F.R.A.; Kudsi, S.Q.; Pereira, G.C.; Fialho, M.F.P.; Lückemeyer, D.D.; Antoniazzi, C.T.d.D.; Landini, L.; Ferreira, J.; Bochi, G.V.; Oliveira, S.M.; De Logu, F.; Nassini, R.; Geppetti, P.; Trevisan, G. Periorbital Nociception in a Progressive Multiple Sclerosis Mouse Model Is Dependent on TRPA1 Channel Activation. Pharmaceuticals 2021, 14, 831. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14080831

AMA Style

Dalenogare DP, Ritter C, Bellinaso FRA, Kudsi SQ, Pereira GC, Fialho MFP, Lückemeyer DD, Antoniazzi CTdD, Landini L, Ferreira J, Bochi GV, Oliveira SM, De Logu F, Nassini R, Geppetti P, Trevisan G. Periorbital Nociception in a Progressive Multiple Sclerosis Mouse Model Is Dependent on TRPA1 Channel Activation. Pharmaceuticals. 2021; 14(8):831. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14080831

Chicago/Turabian Style

Dalenogare, Diéssica P., Camila Ritter, Fernando R.A. Bellinaso, Sabrina Q. Kudsi, Gabriele C. Pereira, Maria F.P. Fialho, Débora D. Lückemeyer, Caren T.d.D. Antoniazzi, Lorenzo Landini, Juliano Ferreira, Guilherme V. Bochi, Sara M. Oliveira, Francesco De Logu, Romina Nassini, Pierangelo Geppetti, and Gabriela Trevisan. 2021. "Periorbital Nociception in a Progressive Multiple Sclerosis Mouse Model Is Dependent on TRPA1 Channel Activation" Pharmaceuticals 14, no. 8: 831. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14080831

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