TRPA1 receptors mediate environmental irritant-induced meningeal vasodilatation

Phillip Edward Kunkler, Carrie Jo Ballard, Gerry Stephen Oxford, Joyce Hurley

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

The TRPA1 receptor is a member of the transient receptor potential (TRP) family of ion channels expressed in nociceptive neurons. TRPA1 receptors are targeted by pungent compounds from mustard and garlic and environmental irritants such as formaldehyde and acrolein. Ingestion or inhalation of these chemical agents causes irritation and burning in the nasal and oral mucosa and respiratory lining. Headaches have been widely reported to be induced by inhalation of environmental irritants, but it is unclear how these agents produce headache. Stimulation of trigeminal neurons releases CGRP and substance P and induces neurogenic inflammation associated with the pain of migraine. Here we test the hypothesis that activation of TRPA1 receptors is the mechanistic link between environmental irritants and peptide-mediated neurogenic inflammation. Known TRPA1 agonists and environmental irritants stimulate CGRP release from dissociated rat trigeminal ganglia neurons and this release is blocked by a selective TRPA1 antagonist, HC-030031. Further, TRPA1 agonists and environmental irritants increase meningeal blood flow following intranasal administration. Prior dural application of the CGRP antagonist, CGRP 8-37, or intranasal or dural administration of HC-030031, blocks the increases in blood flow elicited by environmental irritants. Together these results demonstrate that TRPA1 receptor activation by environmental irritants stimulates CGRP release and increases cerebral blood flow. We suggest that these events contribute to headache associated with environmental irritants.

Original languageEnglish
Pages (from-to)38-44
Number of pages7
JournalPain
Volume152
Issue number1
DOIs
StatePublished - Jan 2011

Fingerprint

Irritants
Vasodilation
Neurogenic Inflammation
Headache
Mustard Compounds
Inhalation
Cerebrovascular Circulation
Acrolein
Neurons
Intranasal Administration
Trigeminal Ganglion
Nociceptors
Garlic
Nasal Mucosa
Mouth Mucosa
Substance P
Migraine Disorders
Ion Channels
Formaldehyde
Eating

Keywords

  • Blood flow
  • CGRP
  • Migraine
  • Sensory neurons
  • Trigeminal ganglia

ASJC Scopus subject areas

  • Clinical Neurology
  • Anesthesiology and Pain Medicine
  • Neurology
  • Pharmacology

Cite this

TRPA1 receptors mediate environmental irritant-induced meningeal vasodilatation. / Kunkler, Phillip Edward; Ballard, Carrie Jo; Oxford, Gerry Stephen; Hurley, Joyce.

In: Pain, Vol. 152, No. 1, 01.2011, p. 38-44.

Research output: Contribution to journalArticle

Kunkler, Phillip Edward ; Ballard, Carrie Jo ; Oxford, Gerry Stephen ; Hurley, Joyce. / TRPA1 receptors mediate environmental irritant-induced meningeal vasodilatation. In: Pain. 2011 ; Vol. 152, No. 1. pp. 38-44.
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