摘要
背景:偏头痛是原发性头痛症。尽管为了了解偏头痛的病理生理学进行了大量的研究,但是仍然有几个方面尚不清楚。三叉血管系统起着关键的作用。神经原性炎症被认为是偏头痛病理生理学中的重要因素,由原代神经元的激活介导,导致各种促炎症神经肽和神经递质例如降钙素基因相关肽(CGRP),P物质(SP),和血管活性肠肽(VIP)。一氧化氮(NO),垂体腺苷酸环化酶激活多肽(PACAP)和谷氨酸(Glu)在调节炎症机制中也起重要作用。 目的:回顾关于偏头痛中与神经源性炎症相关的新型治疗靶点的文献。 方法:在PUBMED数据库中进行系统的文献检索,关于偏头痛的治疗策略,重点放在神经源性炎症期间释放的物质和细胞因子上,直到2017年1月。 结果:使用针对CGRP和CGRP受体的单克隆抗体正在进行的III期临床研究为偏头痛治疗提供了有希望的新颖方面。针对SP和一氧化氮合酶(NOS)的临床前和临床研究全部终止,与安慰剂相比没有显着的结果。新的有希望的治疗目标可能是PACAP及其受体(PAC1)和犬尿酸(KYNA)类似物。 结论:目前的偏头痛治疗只能使一小部分偏头痛患者得到缓解疼痛,并且可能不足以治疗因副作用而导致心血管并发症的患者。因此,对偏头痛病理生理学的更好的理解可能导致在偏头痛发作治疗和预防中的新的治疗线。
关键词: 神经源性炎症,三叉血管系统,降钙素基因相关肽,垂体腺苷酸环化酶激活多肽,犬尿酸,偏头痛。
Current Medicinal Chemistry
Title:Migraine, Neurogenic Inflammation, Drug Development - Pharmacochemical Aspects
Volume: 24 Issue: 33
关键词: 神经源性炎症,三叉血管系统,降钙素基因相关肽,垂体腺苷酸环化酶激活多肽,犬尿酸,偏头痛。
摘要: Background: Migraine is a primary headache disorder. Despite numerous studies conducted with the aim to understand the pathophysiology of migraine, several aspects are still unclear. The trigeminovascular system plays a key role. Neurogenic inflammation is presumed to be an important factor in migraine pathophysiology, mediated by the activation of primary neurons, leading to the release of various pro-inflammatory neuropeptides and neurotransmitters such as Calcitonin Gene-Related Peptide (CGRP), substance P (SP), and vasoactive intestinal peptide (VIP). Nitric oxide (NO), Pituitary adenylate cyclase-activating polypeptide (PACAP) and Glutamate (Glu) also play an important role in the modulation of inflammatory mechanisms.
Objective: To review the literature focusing on novel therapeutic targets in migraine, related to neurogenic inflammation.
Method: A systematic literature search in the database of PUBMED was conducted regarding therapeutic strategies in migraine, focusing on substances and cytokines released during neurogenic inflammation, published until January 2017.
Results: Ongoing phase III clinical studies with monoclonal antibodies against CGRP and CGRP receptors offer promising novel aspects for migraine treatment. Preclinical and clinical studies targeting SP and nitric oxide synthase (NOS) were all terminated with no significant results compared to placebo. New promising therapeutic goal could be PACAP and its receptor (PAC1), and kynurenic acid (KYNA) analogues.
Conclusion: Current migraine treatment offers pain relief only for a small proportion of migraine patients and might not be adequate for patients with cardiovascular comorbidity due to side effects. Better understanding of migraine pathophysiology might, therefore, lead to novel therapeutic lines both in migraine attack treatment and prophylaxis.
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Cite this article as:
Migraine, Neurogenic Inflammation, Drug Development - Pharmacochemical Aspects, Current Medicinal Chemistry 2017; 24 (33) . https://dx.doi.org/10.2174/0929867324666170712163437
DOI https://dx.doi.org/10.2174/0929867324666170712163437 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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