The Department of Biochemistry and Molecular Biology, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA The Department of Pharmacology and Toxicology, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Pain. 2011 Jan;152(1):38-44. doi: 10.1016/j.pain.2010.08.021. Epub 2010 Nov 13.
The TRPA1 receptor is a member of the transient receptor potential (TRP) family of ion channels expressed in nociceptive neurons. TRPA1 receptors are targeted by pungent compounds from mustard and garlic and environmental irritants such as formaldehyde and acrolein. Ingestion or inhalation of these chemical agents causes irritation and burning in the nasal and oral mucosa and respiratory lining. Headaches have been widely reported to be induced by inhalation of environmental irritants, but it is unclear how these agents produce headache. Stimulation of trigeminal neurons releases CGRP and substance P and induces neurogenic inflammation associated with the pain of migraine. Here we test the hypothesis that activation of TRPA1 receptors is the mechanistic link between environmental irritants and peptide-mediated neurogenic inflammation. Known TRPA1 agonists and environmental irritants stimulate CGRP release from dissociated rat trigeminal ganglia neurons and this release is blocked by a selective TRPA1 antagonist, HC-030031. Further, TRPA1 agonists and environmental irritants increase meningeal blood flow following intranasal administration. Prior dural application of the CGRP antagonist, CGRP(8-37), or intranasal or dural administration of HC-030031, blocks the increases in blood flow elicited by environmental irritants. Together these results demonstrate that TRPA1 receptor activation by environmental irritants stimulates CGRP release and increases cerebral blood flow. We suggest that these events contribute to headache associated with environmental irritants.
TRPA1 受体是瞬时受体电位 (TRP) 家族的成员之一，存在于伤害感受神经元中。TRPA1 受体是芥末和大蒜中的刺激性化合物以及甲醛和丙烯醛等环境刺激物的靶点。这些化学物质的摄入或吸入会导致鼻腔和口腔黏膜以及呼吸道内层的刺激和灼烧。广泛报道称，吸入环境刺激物会引起头痛，但这些物质如何引起头痛尚不清楚。三叉神经神经元的刺激会释放 CGRP 和 P 物质，并引起与偏头痛疼痛相关的神经源性炎症。在这里，我们测试了这样一个假设，即 TRPA1 受体的激活是环境刺激物与肽介导的神经源性炎症之间的机制联系。已知的 TRPA1 激动剂和环境刺激物会刺激分离的大鼠三叉神经节神经元释放 CGRP，而这种释放被选择性 TRPA1 拮抗剂 HC-030031 阻断。此外，TRPA1 激动剂和环境刺激物会在鼻内给药后增加脑膜血流量。CGRP 拮抗剂 CGRP(8-37)的预先硬脑膜应用，或 HC-030031 的鼻内或硬脑膜给药，可阻断环境刺激物引起的血流量增加。这些结果共同表明，环境刺激物对 TRPA1 受体的激活刺激了 CGRP 的释放并增加了脑血流量。我们认为这些事件与环境刺激物引起的头痛有关。
