11月3日，据美国媒体报道，被称为头疼树的植物的一股气味就能引发强烈的痛苦，现在科学家知道原因了。这种树的一种成分引发的一系列事件最终刺激了流向大脑外膜的血流。
氯、香烟和甲醛等其他引发头疼的因素与某些相同的细胞构造相互作用，这表明它们都是通过相同的引发痛苦的机制起作用的。
在这项新研究中，一组国际研究人员从干月桂叶中提取了植物化合物加州月桂酮，然后让各种老鼠细胞接触这种化合物。10月27日，研究人员在《脑》刊物的网络版上宣布，加州月桂酮触发了会对酷寒刺激物以及山葵和芥末油的气味起反应的细胞探测器。
研究人员发现，刺激这一化学探测器最终会释放出一种对偏头痛有影响的特殊蛋白质。这种蛋白质会导致血管膨胀，科学家认为血管膨胀会对头骨和神经产生压力，从而引发疼痛。
加利福尼亚大学头疼中心主任、神经科学家彼得·戈德斯比说，其他与头疼有关的刺激物也与同种化学探测器相互作用，把它作为治疗目标或许是个好办法。（生物谷 Bioon.com）
doi:10.1093/brain/awr272
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The ‘headache tree’ via umbellulone and TRPA1 activates the trigeminovascular system
Romina Nassini, Serena Materazzi, Joris Vriens, Jean Prenen, Silvia Benemei, Gaetano De Siena1, Giancarlo la Marca, Eunice Andrè, Delia Preti, Cristina Avonto, Laura Sadofsky, Vincenzo Di Marzo, Luciano De Petrocellis, Greg Dussor, Frank Porreca, Orazio Taglialatela-Scafati, Giovanni Appendino, Bernd Nilius and Pierangelo Geppetti
The California bay laurel or Umbellularia californica (Hook. & Arn.) Nutt., is known as the ‘headache tree’ because the inhalation of its vapours can cause severe headache crises. However, the underlying mechanism of the headache precipitating properties of Umbellularia californica is unknown. The monoterpene ketone umbellulone, the major volatile constituent of the leaves of Umbellularia californica, has irritating properties, and is a reactive molecule that rapidly binds thiols. Thus, we hypothesized that umbellulone stimulates the transient receptor potential ankyrin 1 channel in a subset of peptidergic, nocioceptive neurons, activating the trigeminovascular system via this mechanism. Umbellulone, from µM to sub-mM concentrations, selectively stimulated transient receptor potential ankyrin 1-expressing HEK293 cells and rat trigeminal ganglion neurons, but not untransfected cells or neurons in the presence of the selective transient receptor potential ankyrin 1 antagonist, HC-030031. Umbellulone evoked a calcium-dependent release of calcitonin gene-related peptide from rodent trigeminal nerve terminals in the dura mater. In wild-type mice, umbellulone elicited excitation of trigeminal neurons and released calcitonin gene-related peptide from sensory nerve terminals. These two responses were absent in transient receptor potential ankyrin 1 deficient mice. Umbellulone caused nocioceptive behaviour after stimulation of trigeminal nerve terminals in wild-type, but not transient receptor potential ankyrin 1 deficient mice. Intranasal application or intravenous injection of umbellulone increased rat meningeal blood flow in a dose-dependent manner; a response selectively inhibited by systemic administration of transient receptor potential ankyrin 1 or calcitonin gene-related peptide receptor antagonists. These data indicate that umbellulone activates, through a transient receptor potential ankyrin 1-dependent mechanism, the trigeminovascular system, thereby causing nocioceptive responses and calcitonin gene-related peptide release. Pharmacokinetics of umbellulone, given by either intravenous or intranasal administration, suggest that transient receptor potential ankyrin 1 stimulation, which eventually results in meningeal vasodilatation, may be produced via two different pathways, depending on the dose. Transient receptor potential ankyrin 1 activation may either be caused directly by umbellulone, which diffuses from the nasal mucosa to perivascular nerve terminals in meningeal vessels, or by stimulation of trigeminal endings within the nasal mucosa and activation of reflex pathways. Transient receptor potential ankyrin 1 activation represents a plausible mechanism for Umbellularia californica-induced headache. Present data also strengthen the hypothesis that a series of agents, including chlorine, cigarette smoke, formaldehyde and others that are known to be headache triggers and recently identified as transient receptor potential ankyrin 1 agonists, utilize the activation of this channel on trigeminal nerves to produce head pain.
