Research Division, Research and Innovation (R&I) s.r.l., Padua, Italy.
Mass Spectrometry and Metabolomic Laboratory, Women's and Children's Health Department, University of Padova, Padua, Italy.
Headache. 2019 Oct;59(9):1665-1670. doi: 10.1111/head.13673.
To describe the role of biochemical anomalies of tyrosine (TYR), tryptophan (TRP), and arginine (ARG) metabolism in patients suffering from episodic and chronic cluster headache (CCH).
The pathogenesis of cluster headache (CH) and the process that transforms the episodic into the chronic form are unknown. However, the accompanying symptoms suggest a dysfunction of the sympathetic system and hypothalamus along with anomalies of metabolism of catecholamines, elusive amines, and nitric oxide (NO) metabolism.
We describe the results obtained from the last papers published on this issue. The level of metabolites were analyzed by different high-performance liquid chromatography methods.
In both episodic and CH patients, the levels of dopamine and elusive amines are very elevated. The only biochemical difference found in studies between episodic and chronic cluster was that norepinephrine levels were significantly lower in episodic cluster in comparison to control and chronic subjects. In addition, the levels of ARG, homoarginine, and citrulline, precursors of synthesis of NO, were significantly lower in chronic cluster.
All these results suggest that TYR, TRP, and ARG metabolism is abnormal and may constitute a biochemical fingerprint of CH patients. The increased levels of norepinephrine in chronic cluster constitute a possible cause of chronicity of this primary headache. The high levels of tryptamine and its activity on the central serotoninergic system may explain why the length of CH is brief in comparison to migraine and tension-type headache. The low levels of ARG, homoarginine, and citrulline may be the consequence of high circulating levels of α -agonists, such as epinephrine and norepinephrine, and their biochemical interaction with endothelial trace amine-associated receptor 1 that induces activation of NO synthase, resulting in NO synthesis in the circulation, NO release, intense vasodilation, and as a result, the cluster attack.
描述酪氨酸（TYR）、色氨酸（TRP）和精氨酸（ARG）代谢的生化异常在发作性和慢性丛集性头痛（CCH）患者中的作用。
丛集性头痛（CH）的发病机制以及将发作性转化为慢性形式的过程尚不清楚。然而，伴随的症状表明自主神经系统和下丘脑功能障碍，以及儿茶酚胺、难以捉摸的胺和一氧化氮（NO）代谢的异常。
我们描述了最后发表的关于这个问题的论文的结果。通过不同的高效液相色谱方法分析代谢物的水平。
在发作性和 CH 患者中，多巴胺和难以捉摸的胺的水平都非常高。在发作性和慢性丛集性研究中发现的唯一生化差异是，与对照组和慢性组相比，发作性丛集性患者的去甲肾上腺素水平明显较低。此外，NO 合成前体 ARG、同型精氨酸和瓜氨酸的水平在慢性丛集性中明显较低。
所有这些结果表明，TYR、TRP 和 ARG 代谢异常，可能构成 CH 患者的生化特征。慢性丛集性中去甲肾上腺素水平升高可能是这种原发性头痛慢性化的原因。色胺及其对中枢 5-羟色胺能系统的活性可能解释了为什么 CH 的持续时间比偏头痛和紧张型头痛短。ARG、同型精氨酸和瓜氨酸的低水平可能是由于循环中 α-激动剂（如肾上腺素和去甲肾上腺素）水平升高及其与内皮迹胺相关受体 1 的生化相互作用的结果，这导致循环中 NO 合成酶的激活，导致 NO 的释放、强烈的血管扩张，以及丛集性发作的结果。
