Sensitization of the trigeminovascular system following environmental irritant exposure.
Sensitization of the trigeminovascular system following environmental irritant exposure.
复制标题
DOI：
10.1177/0333102415574845
复制
发表时间：
2015-11
期刊：
影响因子：
--
通讯作者：
Hurley JH
中科院分区：
文献类型：
--
作者：
Kunkler PE;Zhang L;Pellman JJ;Oxford GS;Hurley JH
空气污染与头痛和偏头痛患者急诊室就诊次数增加有关，偏头痛患者经常引用化学物质或气味作为头痛诱因，但空气污染物和头痛之间的联系尚不清楚。我们以前曾报道，鼻腔给药环境刺激物通过TRPA1依赖的机制显著增加脑膜血流量，涉及三叉神经血管系统。在这里，我们研究慢性环境刺激性暴露是否会使三叉神经血管系统敏感。在测量脑膜血流量之前，雄性大鼠吸入TRPA1激动剂丙烯醛或室内空气4天。一些动物在吸入前每天注射TRPA1拮抗剂、AP-18或赋形剂。分离三叉神经节，进行血流免疫细胞化学和/或定量聚合酶链式反应测定TRPV1、TRPA1和CGRP水平。与室内空气相比，丙烯醛吸入可增强对TRPA1和TRPV1激动剂的血流反应。丙烯醛暴露不改变三叉神经节内TRPV1或TRPA1mRNA水平，也不改变TRPV1或CGRP免疫反应细胞数。用AP-18预处理可减弱丙烯醛对TRPA1激动剂的三叉神经血管反应的敏化作用。这些结果表明，三叉神经血管敏化是化学物质暴露后头痛易感性增加的一种机制。
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. Male rats were exposed to acrolein, a TRPA1 agonist, or room air by inhalation for 4 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. Acrolein inhalation exposure potentiated blood flow responses to both 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. These results suggest trigeminovascular sensitization as a mechanism for enhanced headache susceptibility after chemical exposure.