Sensitization of the trigeminovascular system following environmental irritant exposure

Phillip Edward Kunkler, Lujuan Zhang, Jessica Joan Pellman, Gerry Stephen Oxford, Joyce Harts Hurley

Research output: Contribution to journalArticle

16 Scopus citations


Background Air pollution is linked to increased emergency room visits for headache, and migraine patients frequently cite chemicals or odors as headache triggers, but the association between air pollutants and headache is not well understood. We previously reported that nasal administration of environmental irritants acutely increases meningeal blood flow via a TRPA1-dependent mechanism involving the trigeminovascular system. Here, we examine whether chronic environmental irritant exposure sensitizes the trigeminovascular system. Methods Male rats were exposed to acrolein, a TRPA1 agonist, or room air by inhalation for four days prior to meningeal blood flow measurements. Some animals were injected daily with a TRPA1 antagonist, AP-18, or vehicle prior to inhalation exposure. Trigeminal ganglia were isolated following blood flow measurements for immunocytochemistry and/or qPCR determination of TRPV1, TRPA1 and CGRP levels. Results Acrolein inhalation exposure potentiated blood flow responses both to TRPA1 and TRPV1 agonists compared to room air. Acrolein exposure did not alter TRPV1 or TRPA1 mRNA levels or TRPV1 or CGRP immunoreactive cell counts in the trigeminal ganglion. Acrolein sensitization of trigeminovascular responses to a TRPA1 agonist was attenuated by pre-treatment with AP-18. Interpretation These results suggest trigeminovascular sensitization as a mechanism for enhanced headache susceptibility after chemical exposure.

Original languageEnglish (US)
Pages (from-to)1192-1201
Number of pages10
Issue number13
StatePublished - Nov 1 2015


  • Headache
  • TRPA1
  • TRPV1
  • acrolein
  • trigeminal ganglion

ASJC Scopus subject areas

  • Clinical Neurology

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