The role of the transient receptor potential ankyrin type-1 (TRPA1) channel in migraine pain: evaluation in an animal model

  • J Headache Pain. 2017 Sep 7;18(1):94. doi: 10.1186/s10194-017-0804-4.
Chiara Demartini  1  2 ,  Cristina Tassorelli  1  2 ,  Anna Maria Zanaboni  1  2 ,  Germana Tonsi  1  2 ,  Oscar Francesconi  3 ,  Cristina Nativi  3  4 ,  Rosaria Greco  5  6
Affiliations
  • 1. Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Center, "C. Mondino" National Neurological Institute, Pavia, Italy.
  • 2. Department of Brain and Behavioral Sciences University of Pavia, Pavia, Italy.
  • 3. Department of Chemistry 'Ugo Schiff', University of Florence, Florence, Italy.
  • 4. FiorGen, University of Florence, Florence, Italy.
  • 5. Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Center, "C. Mondino" National Neurological Institute, Pavia, Italy. [email protected].
  • 6. IRCCS "National Neurological Institute C. Mondino" Foundation, Via Mondino, 2, 27100, Pavia, Italy. [email protected].
PMID: 28884307 DOI: 10.1186/s10194-017-0804-4
Abstract

Background: Clinical and experimental studies have pointed to the possible involvement of the transient receptor potential ankyrin type-1 (TRPA1) channels in migraine pain. In this study, we aimed to further investigate the role of these channels in an animal model of migraine using a novel TRPA1 antagonist, ADM_12, as a probe.

Methods: The effects of ADM_12 on nitroglycerin-induced hyperalgesia at the trigeminal level were investigated in male rats using the quantification of nocifensive behavior in the orofacial formalin test. The expression levels of the genes coding for c-Fos, TRPA1, Calcitonin gene-related peptide (CGRP) and substance P (SP) in peripheral and central areas relevant for migraine pain were analyzed. CGRP and SP protein immunoreactivity was also evaluated in trigeminal nucleus caudalis (TNC).

Results: In rats bearing nitroglycerin-induced hyperalgesia, ADM_12 showed an anti-hyperalgesic effect in the second phase of the orofacial formalin test. This effect was associated to a significant inhibition of nitroglycerin-induced increase in c-Fos, TRPA1 and neuropeptides mRNA levels in medulla-pons area, in the cervical spinal cord and in the trigeminal ganglion. No differences between groups were seen as regards CGRP and SP protein expression in the TNC.

Conclusions: These findings support a critical involvement of TRPA1 channels in the pathophysiology of migraine, and show their active role in counteracting hyperalgesia at the trigeminal level.

Keywords
Migraine; NTG; TRPA1 antagonist; Trigeminal hyperalgesia.
Products