TRP channels and migraine

The mechanism of migraine, a neurovascular disorder which affects one fifth of the general population and involves patients from infancy through senescence, is still elusive. Poor understanding of the molecular pathways which, activated by a variety of triggering factors, eventually result in the migraine attack, is the main reason for the absence of a satisfactory cure of the disease. However, advancements have been made in the last two decades with the discovery of new drugs for the symptomatic relief of the migraine attack. Indeed, from the early use of non steroidal anti-inflammatory drugs and ergot derivatives, the introduction of triptans (serotonin 5-HT1B/D receptor agonists), and more recently the development of calcitonin gene-related peptide (CGRP) receptor antagonists, is offering an adequate answer to the patient needs for the acute treatment of the pain and associated symptoms of the migraine attack. The release of CGRP from terminals of trigeminal primary sensory neurons is now recognized as a major event of the underlying mechanisms of migraine. Thus, major attention has been paid to the molecular, neurochemical, and anatomical pathways that modulate CGRP release. A variety of receptors and channels are expressed by trigeminal primary sensory neurons, where they regulate neuropeptide release. Among them, the transient receptor potential (TRP) family of cation channels is gaining increasing importance, principally because of the recent discovery of endogenous and exogenous TRP stimulants, which are known inducers of the migraine attack. The present chapter focuses on the description of the TRP channels expressed in the different subpopulations of primary sensory neurons and on their role and relevance in migraine mechanism.