Abstract:

Migraine is a highly prevalent, disabling neurovascular disorder characterized by a combination of headache, nausea and altered sensory processing such as photophobia. Migraine has a strong genetic background but the molecular pathways that result in a migraine attack, and the role of various triggers, are poorly understood. The throbbing and pulsating pain associated with the headache phase of migraine attack implies an important role for the nociceptive activation of trigeminal intracranial afferents that contain calcitonin gene-related peptide (CGRP). Neurogenic inflammation triggered by the release of CGRP is now recognized as a significant underlying event in migraine. Indeed, CGRP receptor antagonists, the so-called “gepants”, have already proved effective in clinical trials as novel, migrainespecific drugs. An alternative therapeutic approach is the modulation of CGRP release. As potential targets, the transient receptor potential (TRP) channels expressed by a subpopulation of CGRP-containing nociceptive primary sensory neurons are gaining increasing prominence, principally because of the recent discovery of a variety of endogenous and exogenous TRP agonists known to induce migraine attack as well as their emerging role in neuropeptide release. The present review focuses on the potential role of the different TRP channels, especially TRPV1, in the migraine mechanism.