{"title":"Orexins and primary headaches: an overview of the neurobiology and clinical impact.","authors":"Emily C Stanyer, Jan Hoffmann, Philip R Holland","doi":"10.1080/14737175.2024.2328728","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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.</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. The authors propose that orexin 1 receptor agonists or positive allosteric modulators should be the focus of future research.</p>","PeriodicalId":12190,"journal":{"name":"Expert Review of Neurotherapeutics","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11034548/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Review of Neurotherapeutics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/14737175.2024.2328728","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/22 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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