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They are involved in an array of functions including homeostatic regulation and nociception, suggesting a potential role in primary headaches.</p><p><strong>Areas covered: </strong>This review summarizes current knowledge of the neurobiology of orexins, their involvement in sleep-wake regulation, nociception, and functions relevant to the associated symptomology of headache disorders. Preclinical reports of the antinociceptive effects of orexin-A in preclinical models are discussed, as well as clinical evidence for the potential involvement of the orexinergic system in headache.</p><p><strong>Expert opinion: </strong>Several lines of evidence support the targeted modulation of orexinergic signaling in primary headaches. Critically, orexins A and B, acting differentially via the orexin 1 and 2 receptors, respectively, demonstrate differential effects on trigeminal pain processing, indicating why dual-receptor antagonists failed to show clinical efficacy. 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引用次数: 0
摘要
导言:包括偏头痛和丛集性头痛在内的原发性头痛是一种发病率很高的疾病,严重影响人们的生活质量。神经影像学研究、发作周期性以及平衡调节的改变等因素表明,下丘脑在头痛中扮演着关键角色。奥曲肽是两种神经肽,几乎只在下丘脑外侧合成,并在中枢神经系统中广泛投射。它们参与了一系列功能,包括平衡调节和痛觉,这表明它们在原发性头痛中可能发挥作用:本综述概述了目前有关奥曲肽神经生物学的知识、奥曲肽参与睡眠-觉醒调节的情况、痛觉以及与头痛疾病症状相关的功能。文章讨论了在临床前模型中奥曲肽-A抗痛觉作用的临床前报告,以及奥曲肽能系统可能参与头痛的临床证据:有多种证据支持对原发性头痛中的奥曲肽能信号进行有针对性的调节。重要的是,奥曲肽 A 和 B 分别通过奥曲肽 1 和 2 受体发挥不同的作用,对三叉神经疼痛处理产生不同的影响,这也说明了为什么双受体拮抗剂未能显示出临床疗效。作者建议,奥曲肽 1 受体激动剂或正异位调节剂应成为未来研究的重点。
Orexins and primary headaches: an overview of the neurobiology and clinical impact.
Introduction: Primary headaches, including migraines and cluster headaches, are highly prevalent disorders that significantly impact quality of life. Several factors suggest a key role for the hypothalamus, including neuroimaging studies, attack periodicity, and the presence of altered homeostatic regulation. The orexins are two neuropeptides synthesized almost exclusively in the lateral hypothalamus with widespread projections across the central nervous system. They are involved in an array of functions including homeostatic regulation and nociception, suggesting a potential role in primary headaches.
Areas covered: This review summarizes current knowledge of the neurobiology of orexins, their involvement in sleep-wake regulation, nociception, and functions relevant to the associated symptomology of headache disorders. Preclinical reports of the antinociceptive effects of orexin-A in preclinical models are discussed, as well as clinical evidence for the potential involvement of the orexinergic system in headache.
Expert opinion: Several lines of evidence support the targeted modulation of orexinergic signaling in primary headaches. Critically, orexins A and B, acting differentially via the orexin 1 and 2 receptors, respectively, demonstrate differential effects on trigeminal pain processing, indicating why dual-receptor antagonists failed to show clinical efficacy. The authors propose that orexin 1 receptor agonists or positive allosteric modulators should be the focus of future research.
期刊介绍:
Expert Review of Neurotherapeutics (ISSN 1473-7175) provides expert reviews on the use of drugs and medicines in clinical neurology and neuropsychiatry. Coverage includes disease management, new medicines and drugs in neurology, therapeutic indications, diagnostics, medical treatment guidelines and neurological diseases such as stroke, epilepsy, Alzheimer''s and Parkinson''s.
Comprehensive coverage in each review is complemented by the unique Expert Review format and includes the following sections:
Expert Opinion - a personal view of the data presented in the article, a discussion on the developments that are likely to be important in the future, and the avenues of research likely to become exciting as further studies yield more detailed results
Article Highlights – an executive summary of the author’s most critical points