title: 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.
authors.affiliation: Clinical Pharmacology Unit, Department of Health Sciences, University of Florence, Florence, Italy; Headache Centre, Department of Health Sciences, University of Florence, Florence, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Benemei
authors.forename: C
authors.initials: C
authors.lastname: Fusi
authors.forename: Gabriela
authors.initials: G
authors.lastname: Trevisan
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Geppetti
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D008024:Ligands; D049990:Membrane Transport Modulators / Q000627:therapeutic use*; D008881:Migraine Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D058990:Molecular Targeted Therapy; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D058748:Pain Perception / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000700:Analgesics; D015220:Calcium Channels; D008024:Ligands; D049990:Membrane Transport Modulators; D009419:Nerve Tissue Proteins; D018015:Receptors, Calcitonin Gene-Related Peptide; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels; D015740:Calcitonin Gene-Related Peptide
keywords: calcitonin gene-related peptide (CGRP); headache; migraine; neurogenic inflammation; neuropathic pain; oxidative stress; sensitization; thermoTRP; transient receptor potential ankyrin 1 (TRPA1)