Faculty of Health Sciences and Social Studies, University of Szeged, Temesvári krt. 31, H-6726 Szeged, Hungary.
ELKH-SZTE Neuroscience Research Group, University of Szeged, H-6725 Szeged, Hungary.
Cells. 2022 Nov 27;11(23):3795. doi: 10.3390/cells11233795.
Migraine is a complex neurovascular disorder, which causes intense socioeconomic problems worldwide. The pathophysiology of disease is enigmatic; accordingly, therapy is not sufficient. In recent years, migraine research focused on tryptophan, which is metabolized via two main pathways, the serotonin and kynurenine pathways, both of which produce neuroactive molecules that influence pain processing and stress response by disturbing neural and brain hypersensitivity and by interacting with molecules that control vascular and inflammatory actions. Serotonin has a role in trigeminal pain processing, and melatonin, which is another product of this pathway, also has a role in these processes. One of the end products of the kynurenine pathway is kynurenic acid (KYNA), which can decrease the overexpression of migraine-related neuropeptides in experimental conditions. However, the ability of KYNA to cross the blood-brain barrier is minimal, necessitating the development of synthetic analogs with potentially better pharmacokinetic properties to exploit its therapeutic potential. This review summarizes the main translational and clinical findings on tryptophan metabolism and certain neuropeptides, as well as therapeutic options that may be useful in the prevention and treatment of migraine.
偏头痛是一种复杂的神经血管性疾病，在全球范围内造成严重的社会经济问题。该疾病的病理生理学机制尚不清楚，因此治疗效果并不理想。近年来，偏头痛的研究集中在色氨酸上，其通过两条主要途径代谢，即 5-羟色胺途径和犬尿氨酸途径，这两条途径都会产生神经活性分子，通过干扰神经和大脑的高敏感性，并与控制血管和炎症反应的分子相互作用，从而影响疼痛处理和应激反应。5-羟色胺在三叉神经疼痛处理中起作用，而该途径的另一种产物褪黑素也在这些过程中起作用。犬尿氨酸途径的终产物之一是犬尿氨酸（KYNA），它可以减少实验条件下与偏头痛相关的神经肽的过度表达。然而，KYNA 穿过血脑屏障的能力非常有限，因此需要开发具有潜在更好药代动力学特性的合成类似物来利用其治疗潜力。本文综述了色氨酸代谢和某些神经肽的主要转化和临床研究结果，以及可能有助于偏头痛预防和治疗的治疗选择。
