The TRPA1 channel in migraine mechanism and treatment

Br J Pharmacol. 2014 May;171(10):2552-67. doi: 10.1111/bph.12512.

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.

Keywords: calcitonin gene-related peptide (CGRP); headache; migraine; neurogenic inflammation; neuropathic pain; oxidative stress; sensitization; thermoTRP; transient receptor potential ankyrin 1 (TRPA1).

Publication types

  • Review

MeSH terms

  • Analgesics / therapeutic use*
  • Animals
  • Calcitonin Gene-Related Peptide / metabolism
  • Calcium Channels / metabolism
  • Drug Design
  • Humans
  • Ligands
  • Membrane Transport Modulators / therapeutic use*
  • Migraine Disorders / drug therapy*
  • Migraine Disorders / metabolism
  • Migraine Disorders / physiopathology
  • Migraine Disorders / psychology
  • Molecular Targeted Therapy
  • Nerve Tissue Proteins / antagonists & inhibitors*
  • Nerve Tissue Proteins / metabolism
  • Pain Perception / drug effects
  • Pain Threshold / drug effects
  • Receptors, Calcitonin Gene-Related Peptide / metabolism
  • TRPA1 Cation Channel
  • Transient Receptor Potential Channels / antagonists & inhibitors*
  • Transient Receptor Potential Channels / metabolism

Substances

  • Analgesics
  • Calcium Channels
  • Ligands
  • Membrane Transport Modulators
  • Nerve Tissue Proteins
  • Receptors, Calcitonin Gene-Related Peptide
  • TRPA1 Cation Channel
  • TRPA1 protein, human
  • Transient Receptor Potential Channels
  • Calcitonin Gene-Related Peptide