11月3日,，據(jù)美國(guó)媒體報(bào)道,，被稱為頭疼樹(shù)的植物的一股氣味就能引發(fā)強(qiáng)烈的痛苦，現(xiàn)在科學(xué)家知道原因了,。這種樹(shù)的一種成分引發(fā)的一系列事件最終刺激了流向大腦外膜的血流,。
氯、香煙和甲醛等其他引發(fā)頭疼的因素與某些相同的細(xì)胞構(gòu)造相互作用,，這表明它們都是通過(guò)相同的引發(fā)痛苦的機(jī)制起作用的,。
在這項(xiàng)新研究中，一組國(guó)際研究人員從干月桂葉中提取了植物化合物加州月桂酮,，然后讓各種老鼠細(xì)胞接觸這種化合物,。10月27日，研究人員在《腦》刊物的網(wǎng)絡(luò)版上宣布,，加州月桂酮觸發(fā)了會(huì)對(duì)酷寒刺激物以及山葵和芥末油的氣味起反應(yīng)的細(xì)胞探測(cè)器,。
研究人員發(fā)現(xiàn)，刺激這一化學(xué)探測(cè)器最終會(huì)釋放出一種對(duì)偏頭痛有影響的特殊蛋白質(zhì),。這種蛋白質(zhì)會(huì)導(dǎo)致血管膨脹,，科學(xué)家認(rèn)為血管膨脹會(huì)對(duì)頭骨和神經(jīng)產(chǎn)生壓力，從而引發(fā)疼痛,。
加利福尼亞大學(xué)頭疼中心主任,、神經(jīng)科學(xué)家彼得·戈德斯比說(shuō)，其他與頭疼有關(guān)的刺激物也與同種化學(xué)探測(cè)器相互作用,，把它作為治療目標(biāo)或許是個(gè)好辦法,。（生物谷 Bioon.com）
doi:10.1093/brain/awr272
PMC:
PMID:
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.
