Induction of chronic migraine phenotypes in a rat model after environmental irritant exposure

Abstract

Air pollution is linked to increased emergency department 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 chronic environmental irritant exposure sensitizes the trigeminovascular system response to nasal administration of environmental irritants. Here, we examine whether chronic environmental irritant exposure induces migraine behavioral phenotypes. Male rats were exposed to acrolein, a transient receptor potential channel ankyrin-1 (TRPA1) agonist, or room air by inhalation for 4 days before meningeal blood flow measurements, periorbital cutaneous sensory testing, or other behavioral testing. Touch-induced c-Fos expression in trigeminal nucleus caudalis was compared in animals exposed to room air or acrolein. Spontaneous behavior and olfactory discrimination was examined in open-field testing. Acrolein inhalation exposure produced long-lasting potentiation of blood flow responses to a subsequent TRPA1 agonist and sensitized cutaneous responses to mechanical stimulation. C-Fos expression in response to touch was increased in trigeminal nucleus caudalis in animals exposed to acrolein compared with room air. Spontaneous activity in an open-field and scent preference behavior was different in acrolein-exposed compared with room air-exposed animals. Sumatriptan, an acute migraine treatment blocked acute blood flow changes in response to TRPA1 or transient receptor potential vanilloid receptor-1 agonists. Pretreatment with valproic acid, a prophylactic migraine treatment, attenuated the enhanced blood flow responses observed after acrolein inhalation exposures. Environmental irritant exposure yields an animal model of chronic migraine in which to study mechanisms for enhanced headache susceptibility after chemical exposure.

Role of intraganglionic transmission in the trigeminovascular pathway

“…52 Other effectors may include endogenous lipids, the most well-known of which is anandamide, a TRPV1 and CB(1) receptor agonist 53 and other lipids recently identified as TRP agonists. 54 In addition to inducing trigeminal sensitization and chronic migraine phenotypes in our animal model, 19,20 acrolein exposure induced changes in several endocannabinoids, including anandamide, in trigeminal tissue. 55 Indeed, interactions between endocannabinoids and TRP channels are strongly implicated in pain 53 and particularly migraine.…”

Effect of dibenz(b,f)-1,4-oxazepine aerosol on the breathing pattern and respiratory variables by continuous recording and analysis in unanaesthetised mice

“…Occupational and environmental exposure to irritating chemicals and inflammatory mediators can produce cough [ 19 ]. Accidental exposure to high concentrations or chronic environmental irritant exposure may sensitise the trigemino-vascular system and cause headache and migraine [ 20 ]. Low concentrations of irritant chemicals produce decrease in respiratory frequency.…”

Current Evidence on the Role of Epigenetic Mechanisms in Migraine: The Way Forward to Precision Medicine

“…Although few studies [119,120] have examined whether environmental irritant exposures induce migraine behavioral phenotypes, the results from these studies suggest that inhalation exposure to environmental irritants induces trigeminovascular and central nervous system sensitization, reproducing some features of chronic migraine models [119,120]. These studies highlight that TRPA1 receptors have important roles in migraine and that they could be targeted for therapeutic purposes [119,121]. Lipid signaling may be another potential mechanism by which repeated exposure to acrolein may drive trigeminovascular sensitization [120].…”