一项荟萃分析显示，丛集性头痛、偏头痛都与昼夜节律系统密切相关。
2023 年 3 月 29 日在线发表在美国神经病学学会（American Academy of Neurology）期刊《神经病学》（Neurology）上的一项荟萃分析显示，丛集性头痛和偏头痛都与身体的内部时钟——昼夜节律系统有密切联系。
这项荟萃分析包括现有可用的所有关于丛集性头痛和偏头痛的昼夜节律特征相关研究。这包括患者一天中和一年中头痛发作时间的信息，以及与生物钟相关的基因（突变）在这些头痛患者中是否更常见的研究。
研究人员还关注了与丛集性头痛、偏头痛以及昼夜节律系统相关的激素的研究，包括皮质醇和褪黑素。
“数据表明，这两种头痛疾病在多个层面上都具有高度的昼夜节律性，尤其是丛集性头痛，”这项研究的作者、美国神经病学会会员、美国得克萨斯大学健康科学中心（University of Texas Health Science Center）的医学博士 Mark Joseph Burish 表示，“下丘脑是大脑中容纳主要生物钟的区域，研究提高了它在丛集性头痛和偏头痛发作过程中的重要性。这项研究还揭示了关于头痛触发因素的遗传学问题，如睡眠变化等，这些是已知的偏头痛触发因素，也是人体昼夜节律的线索。”
这项荟萃分析发现，丛集性头痛中有 71% 遵循昼夜节律模式，在深夜或凌晨达到发作顶峰，并且在春秋两季发病更多。从基因水平来看，这类头痛与 2 个主要昼夜节律基因有关，此外 9 个可能增加丛集性头痛易感性的基因中有 5 个都具有昼夜节律表达模式。
与不患有丛集性头痛的人相比，患丛集性头痛的人皮质醇水平较高，褪黑素水平较低。
对于偏头痛，荟萃分析显示有 50% 的发作遵循昼夜节律模式。虽然偏头痛在白天的发作时间范围很广，从早上到傍晚都有，但夜间有个节律性的发作低点。偏头痛同样与 2 个主要的昼夜节律基因相关，在与偏头痛相关的 168 个基因中有 110 个具有昼夜节律的表达模式。
偏头痛患者尿液中的褪黑素水平低于非偏头痛患者。此外，褪黑素水平在偏头痛发作期间也会变得更低。
“这些结论有望提高使用基于昼夜节律的疗法治疗头痛的可能性，”Burish 说，“这可能既包括基于昼夜节律的治疗——例如在一天中的特定时间服用药物，还可以使用某些能够引起昼夜节律变化的药物来进行治疗。”
不过这项研究的局限性在于，研究人员没有将那些可能影响昼夜节律的因素考虑在内，例如药物、双相情感障碍等其他疾病，以及夜班工作等昼夜节律问题。
这项研究得到了 Will Erwin 头痛研究基金会的支持。
想了解更多关于头痛的信息可以登录 BrainandLife.org，该网站是美国神经病学会免费向患者和护理人员提供杂志的网站，该杂志专注于神经系统疾病与大脑健康的交叉研究。
原文链接：
https://www.eurekalert.org/news-releases/983834
论文信息
【标题】Circadian Features of Cluster Headache and Migraine: A Systematic Review, Meta-analysis, and Genetic Analysis
【作者】 Barlas Benkli, Sun Young Kim, Nobuya Koike, Chorong Han, Celia Tran, Emma Silva, Yuanqing Yan, Kazuhiro Yagita, Zheng Chen, Seung-Hee Yoo, Mark Joseph Burish
【期刊】Neurology
【日期】29 March 2023
【DOI】 https://doi.org/10.1212/WNL.0000000000207240
【摘要】Background and objectives: Cluster headache and migraine have circadian features at multiple levels (cellular, systems, and behavioral). A thorough understanding of their circadian features informs their pathophysiologies.
Methods: A librarian created search criteria in Medline Ovid, Embase, PsycINFO, Web of Science, and Cochrane Library. Two physicians independently performed the remainder of the systematic review/meta-analysis using PRISMA guidelines. Separate from the systematic review/meta-analysis we performed a genetic analysis for genes with a circadian pattern of expression (Clock Controlled Genes or CCGs) by cross-referencing genome-wide association studies (GWAS) of headache, a non-human primate study of CCGs in a variety of tissues, and recent reviews of brain areas relevant in headache disorders. Altogether, this allowed us to catalog circadian features at the behavioral level (circadian timing, time of day, time of year, and chronotype), systems level (relevant brain areas where CCGs are active, melatonin and corticosteroid levels), and cellular level (core circadian genes and CCGs).
Results: For the systematic review and meta-analysis, 1513 studies were found and 72 met inclusion criteria; for the genetic analysis we found 16 GWAS, 1 non-human primate study, and 16 imaging reviews.
Cluster headache: Behaviorally, meta-analyses showed a circadian pattern of attacks in 70.5% (3490/4953) of participants across 16 studies, with a clear circadian peak between 21:00-03:00 and circannual peaks in spring and autumn. Chronotype was highly variable across studies. At the systems level, lower melatonin and higher cortisol levels were reported. At the cellular level, cluster headache was associated with core circadian genes CLOCK and REV-ERBα, and five of the nine cluster headache susceptibility genes were CCGs.
Migraine: Behaviorally, meta-analyses showed a circadian pattern of attacks in 50.1% (2698/5385) of participants across eight studies, with a clear circadian trough between 23:00-07:00 and a broad circannual peak between April-October. Chronotype was highly variable across studies. At the systems level, urinary melatonin levels were lower in migraine participants and even lower during an attack. At the cellular level, migraine was associated with core circadian genes CK1δ and RORα, and 110 of the 168 migraine susceptibility genes were CCGs.
Discussion: Cluster headache and migraine are highly circadian at multiple levels, reinforcing the importance of the hypothalamus. This review provides a pathophysiological foundation for circadian-targeted research into these disorders.
Trial Registration Information: The study was registered with PROSPERO (registration number CRD42021234238).
【链接】
https://n.neurology.org/content/early/2023/03/29/WNL.0000000000207240
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