TRPA1 and other TRP channels in migraine

Silvia Benemei, Francesco De Cesaris, Camilla Fusi, Eleonora Rossi, Chiara Lupi, Pierangelo Geppetti

Ever since their identification, interest in the role of transient receptor potential (TRP) channels in health and disease has steadily increased. Robust evidence has underlined the role of TRP channels expressed in a subset of primary sensory neurons of the trigeminal ganglion to promote, by neuronal excitation, nociceptive responses, allodynia and hyperalgesia. In particular, the TRP vanilloid 1 (TRPV1) and the TRP ankyrin 1 (TRPA1) are expressed in nociceptive neurons, which also express the sensory neuropeptides, tachykinins, and calcitonin gene-related peptide (CGRP), which mediate neurogenic inflammatory responses. Of interest, CGRP released from the trigeminovascular network of neurons is currently recognized as a main contributing mechanism of migraine attack. The ability of TRPA1 to sense and to be activated by an unprecedented series of exogenous and endogenous reactive molecules has now been extensively documented. Several of the TRPA1 activators are also known as triggers of migraine attack. Thus, TRP channels, and particularly TRPA1, may be proposed as novel pathways in migraine pathophysiology and as possible new targets for its treatment.