The TRPA1 channel in inflammatory and neuropathic pain and migraine

Rev Physiol Biochem Pharmacol. 2014;167:1-43. doi: 10.1007/112_2014_18.


The transient receptor potential ankyrin 1 (TRPA1), a member of the TRP superfamily of channels, is primarily localized to a subpopulation of primary sensory neurons of the trigeminal, vagal, and dorsal root ganglia. This subset of nociceptors produces and releases the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP), which mediate neurogenic inflammatory responses. TRPA1 is activated by a number of exogenous compounds, including molecules of botanical origin, environmental irritants, and medicines. However, the most prominent feature of TRPA1 resides in its unique sensitivity for large series of reactive byproducts of oxidative and nitrative stress. Here, the role of TRPA1 in models of different types of pain, including inflammatory and neuropathic pain and migraine, is summarized. Specific attention is paid to TRPA1 as the main contributing mechanism to the transition of mechanical and cold hypersensitivity from an acute to a chronic condition and as the primary transducing pathway by which oxidative/nitrative stress produces acute nociception, allodynia, and hyperalgesia. A series of migraine triggers or medicines have been reported to modulate TRPA1 activity and the ensuing CGRP release. Thus, TRPA1 antagonists may be beneficial in the treatment of inflammatory and neuropathic pain and migraine.

Publication types

  • Review

MeSH terms

  • Animals
  • Calcium Channels / chemistry
  • Calcium Channels / physiology*
  • Humans
  • Inflammation / drug therapy
  • Inflammation / etiology*
  • Migraine Disorders / drug therapy
  • Migraine Disorders / etiology*
  • Nerve Tissue Proteins / agonists
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / physiology*
  • Neuralgia / drug therapy
  • Neuralgia / etiology*
  • Nociceptors / physiology
  • TRPA1 Cation Channel
  • Transient Receptor Potential Channels / agonists
  • Transient Receptor Potential Channels / antagonists & inhibitors
  • Transient Receptor Potential Channels / chemistry
  • Transient Receptor Potential Channels / physiology*


  • Calcium Channels
  • Nerve Tissue Proteins
  • TRPA1 Cation Channel
  • TRPA1 protein, human
  • Transient Receptor Potential Channels