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Cephalalgia. 2015 Nov;35(13):1192-201. doi: 10.1177/0333102415574845. Epub 2015 Feb 27.

Sensitization of the trigeminovascular system following environmental irritant exposure.

Author information

1
The Department of Biochemistry and Molecular Biology, Stark Neurosciences Research Institute, Indiana University School of Medicine, USA.
2
The Department of Pharmacology and Toxicology, Stark Neurosciences Research Institute, Indiana University School of Medicine, USA.
3
The Department of Biochemistry and Molecular Biology, Stark Neurosciences Research Institute, Indiana University School of Medicine, USA johurley@iupui.edu.

Abstract

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.

KEYWORDS:

Headache; TRPA1; TRPV1; acrolein; trigeminal ganglion

PMID:
25724913
PMCID:
PMC4918469
DOI:
10.1177/0333102415574845
[Indexed for MEDLINE]
Free PMC Article

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