Pharmaceuticals (Aug 2021)

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

  • Diéssica Padilha Dalenogare,
  • Camila Ritter,
  • Fernando Roberto Antunes Bellinaso,
  • Sabrina Qader Kudsi,
  • Gabriele Cheiran Pereira,
  • Maria Fernanda Pessano Fialho,
  • Débora Denardin Lückemeyer,
  • Caren Tatiane de David Antoniazzi,
  • Lorenzo Landini,
  • Juliano Ferreira,
  • Guilherme Vargas Bochi,
  • Sara Marchesan Oliveira,
  • Francesco De Logu,
  • Romina Nassini,
  • Pierangelo Geppetti,
  • Gabriela Trevisan

DOI
https://doi.org/10.3390/ph14080831
Journal volume & issue
Vol. 14, no. 8
p. 831

Abstract

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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.

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