Sensitization of the trigeminovascular system following environmental irritant exposure.
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.


CONCLUSIONS
These results suggest trigeminovascular sensitization as a mechanism for enhanced headache susceptibility after chemical exposure.
The Department of Biochemistry and Molecular Biology, Stark Neurosciences Research Institute, Indiana University School of Medicine, USA.
Phillip Edward
PE
Kunkler
The Department of Biochemistry and Molecular Biology, Stark Neurosciences Research Institute, Indiana University School of Medicine, USA.
LuJuan
L
Zhang
The Department of Pharmacology and Toxicology, Stark Neurosciences Research Institute, Indiana University School of Medicine, USA.
Jessica Joan
JJ
Pellman
The Department of Pharmacology and Toxicology, Stark Neurosciences Research Institute, Indiana University School of Medicine, USA.
Gerry Stephen
GS
Oxford
The Department of Biochemistry and Molecular Biology, Stark Neurosciences Research Institute, Indiana University School of Medicine, USA johurley@iupui.edu.
Joyce Harts
JH
Hurley
D000171:Acrolein / Q000633:toxicity*; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects* / Q000502:physiology; D004781:Environmental Exposure / Q000009:adverse effects*; D019570:Inhalation Exposure / Q000009:adverse effects; D007509:Irritants / Q000633:toxicity*; D008297:Male; D010091:Oximes / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012668:Trigeminal Ganglion / Q000098:blood supply* / Q000187:drug effects* / Q000502:physiology
C000602225:4-(4-chlorophenyl)-3-methylbut-3-en-2-oxime; D007509:Irritants; D010091:Oximes; D000171:Acrolein
Headache; TRPA1; TRPV1; acrolein; trigeminal ganglion