The TRPA1 channel in migraine mechanism and treatment

Abstract

Migraine remains an elusive and poorly understood disease. The uncertainty is reflected by the currently unsatisfactory acute and prophylactic treatments for this disease. Genetic and pharmacological information points to the involvement of some transient receptor potential (TRP) channels in pain mechanisms. In particular, the TRP vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) channels seem to play a major role in different models of pain diseases. Recent findings have underscored the possibility that TRP channels expressed in the nerve terminals of peptidergic nociceptors contribute to the migraine mechanism. Among this channel subset, TRPA1, a sensor of oxidative, nitrative and electrophilic stress, is activated by an unprecedented series of irritant and pain-provoking exogenous and endogenous agents, which release the pro-migraine peptide, calcitonin gene-related peptide, through this neuronal pathway. Some of the recently identified TRPA1 activators have long been known as migraine triggers. Furthermore, specific analgesic and antimigraine medicines have been shown to inhibit or desensitize TRPA1 channels. Thus, TRPA1 is emerging as a major contributing pathway in migraine and as a novel target for the development of drugs for pain and migraine treatment. LINKED ARTICLESThis article is part of a themed section on the pharmacology of TRP channels. To view the other articles in this section visit http://dx

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…The role of vanilloid transient receptor potential 1 in migraine and cluster headache. Migraine is a common, debilitating episodic disorder characterized by unilateral throbbing headache, phonophobia, photophobia, and nausea, which is sometimes preceded by premonitory symptoms (so-called "aura") (reviewed in Nassini et al, 2010a;Benemei et al, 2013). For unclear reasons (that may include the hormonal milieu), migraine is more common in women (18%) than in men (6%).…”

“…There is good evidence that activation by irritants of TRPA1 receptors at trigeminal nerve terminals in the nasal mucosa and subsequent activation of the trigeminovascular system play an important role in air pollution-induced headache (see Nassini et al, 2013;Oxford and Hurley, 2013). Studies on the potential role of TRPA1 in migraine are, however, still in their infancy (reviewed in Benemei et al, 2013).…”

Diet and nutraceutical interventions for headache management: A review of the evidence

“…Parthenolide, a sesquiterpene lactone, appears to be feverfew's active ingredient and has multiple actions in the central nervous system. Several of its properties suggest a potential mechanism of action in migraine prevention, including evidence to suggest that parthenolide inhibits Fos-induced 8 Cephalalgia 0(0) activation of the nucleus trigeminalis caudalis (57), a nucleus central to migraine pathogenesis, and evidence for partial agonist activity of parthenolide at TRPA1 channels (58), which have been implicated in migraine pathogenesis (59). Feverfew is one of the best-studied nutraceutical agents for migraine prophylaxis in adults.…”

Diet-induced obesity alters dural CGRP release and potentiates TRPA1-mediated trigeminovascular responses

“…Further, activation of nasal mucosal trigeminal afferents which express the TRPA1 receptor has been suggested as a pathophysiological mechanism involved in the generation of headache induced by inhaled environmental irritants (15). The TRPA1 agonist acrolein is a component of tobacco smoke, vehicle exhaust and vapours of overheated cooking oils, which along with other TRPA1 agonists are known triggers of migraine attacks in susceptible individuals (16,17). Importantly, prolonged exposure to acrolein through inhalation has been demonstrated to sensitise the trigeminovascular system (18).…”