The role of kynurenines in migraine-related neuroimmune pathways.

IF 7.3 1区 医学 Q1 CLINICAL NEUROLOGY
Tamás Körtési, Gábor Nagy-Grócz, László Vécsei
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引用次数: 0

Abstract

Migraine, a primary headache disorder whose mechanism remains incompletely understood, appears to involve the activation of the trigeminovascular system (TS) during attacks. Research suggests that inflammatory processes mediated by the immune system may play a role in migraine pathophysiology. Neuroinflammation is often associated with migraine attacks, with cytokines serving as crucial mediators in the process. Elevated levels of pro-inflammatory cytokines, such as interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), have been observed in the blood and cerebrospinal fluid of individuals experiencing migraine attacks. These cytokines have the capacity to sensitize pain pathways in the brain, thereby increasing sensitivity to pain stimuli. This phenomenon, known as central sensitization, is believed to contribute to the intensity and persistence of migraine pain. Kynurenines, endogenous mediators of glutamatergic mechanisms, can significantly influence the pathophysiology of primary headache disorders. The kynurenine system is collectively known as the kynurenine pathway (KP), which can act on multiple receptors, such as glutamate receptors, aryl hydrocarbon receptors (AhRs), G protein-coupled receptors 35 (GPR35), and α-7 nicotinic acetylcholine (α7 nACh) receptors. These receptors are also found on various cells of the immune system, so the role of the KP in the pathomechanism of primary headaches may also be mediated through them. In this review, our goal is to show a possible link between the receptors of the KP and immune system in the context of inflammation and migraine. Migraine research in recent years has focused on neuropeptides, such as calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) as potential pathogenic factors and possible therapeutic approaches. These peptides share many similarities in their characteristics and roles. For instance, they exhibit potent vasodilation, occur in both the peripheral and central nervous systems, and play a role in transmitting nociception and neurogenic inflammation. The investigation of potential connections between the aforementioned neuropeptides and the kynurenine pathway could play a significant role in uncovering the pathomechanism of migraine and identifying new drug candidates.

犬尿氨酸在偏头痛相关神经免疫通路中的作用。
偏头痛是一种原发性头痛疾病,其发病机制尚不完全清楚,似乎涉及发作时三叉神经血管系统(TS)的激活。研究表明,免疫系统介导的炎症过程可能在偏头痛的病理生理学中发挥作用。神经炎症通常与偏头痛发作有关,细胞因子是这一过程中的关键介质。在偏头痛发作患者的血液和脑脊液中,已观察到白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)等促炎细胞因子水平升高。这些细胞因子能够使大脑中的疼痛通路变得敏感,从而增加对疼痛刺激的敏感性。这种现象被称为 "中枢敏化"(central sensitization),被认为是导致偏头痛剧烈和持续的原因。犬尿氨酸是谷氨酸能机制的内源性介质,可对原发性头痛疾病的病理生理学产生重大影响。犬尿氨酸系统统称为犬尿氨酸途径(KP),可作用于多种受体,如谷氨酸受体、芳基烃受体(AhRs)、G 蛋白偶联受体 35(GPR35)和α-7 烟碱乙酰胆碱(α7 nACh)受体。这些受体也存在于免疫系统的各种细胞中,因此 KP 在原发性头痛的病理机制中的作用也可能是通过它们介导的。在这篇综述中,我们的目标是在炎症和偏头痛的背景下说明 KP 受体与免疫系统之间可能存在的联系。近年来,偏头痛研究的重点是神经肽,如降钙素基因相关肽(CGRP)和垂体腺苷酸环化酶激活多肽(PACAP),将其作为潜在的致病因素和可能的治疗方法。这些肽的特性和作用有许多相似之处。例如,它们具有强效的血管扩张作用,同时存在于外周和中枢神经系统中,并在痛觉传导和神经源性炎症中发挥作用。研究上述神经肽与犬尿氨酸通路之间的潜在联系,可在揭示偏头痛的病理机制和确定新的候选药物方面发挥重要作用。
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来源期刊
Journal of Headache and Pain
Journal of Headache and Pain 医学-临床神经学
CiteScore
11.80
自引率
13.50%
发文量
143
审稿时长
6-12 weeks
期刊介绍: The Journal of Headache and Pain, a peer-reviewed open-access journal published under the BMC brand, a part of Springer Nature, is dedicated to researchers engaged in all facets of headache and related pain syndromes. It encompasses epidemiology, public health, basic science, translational medicine, clinical trials, and real-world data. With a multidisciplinary approach, The Journal of Headache and Pain addresses headache medicine and related pain syndromes across all medical disciplines. It particularly encourages submissions in clinical, translational, and basic science fields, focusing on pain management, genetics, neurology, and internal medicine. The journal publishes research articles, reviews, letters to the Editor, as well as consensus articles and guidelines, aimed at promoting best practices in managing patients with headaches and related pain.
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