Department of Basic and Clinical Neuroscience, Headache Group, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Department of Clinical Physiology, Nuclear Medicine and PET, 70590 Rigshospitalet, Copenhagen, Denmark.
J Headache Pain. 2018 Mar 5;19(1):20. doi: 10.1186/s10194-018-0844-4.
The interaction between sleep and primary headaches has gained considerable interest due to their strong, bidirectional, clinical relationship. Several primary headaches demonstrate either a circadian/circannual rhythmicity in attack onset or are directly associated with sleep itself. Migraine and cluster headache both show distinct attack patterns and while the underlying mechanisms of this circadian variation in attack onset remain to be fully explored, recent evidence points to clear physiological, anatomical and genetic points of convergence. The hypothalamus has emerged as a key brain area in several headache disorders including migraine and cluster headache. It is involved in homeostatic regulation, including pain processing and sleep regulation, enabling appropriate physiological responses to diverse stimuli. It is also a key integrator of circadian entrainment to light, in part regulated by pituitary adenylate cyclase-activating peptide (PACAP). With its established role in experimental headache research the peptide has been extensively studied in relation to headache in both humans and animals, however, there are only few studies investigating its effect on sleep in humans. Given its prominent role in circadian entrainment, established in preclinical research, and the ability of exogenous PACAP to trigger attacks experimentally, further research is very much warranted. The current review will focus on the role of the hypothalamus in the regulation of sleep-wake and circadian rhythms and provide suggestions for the future direction of such research, with a particular focus on PACAP.
由于睡眠与原发性头痛之间存在密切的临床关系，两者之间的相互作用引起了广泛关注。一些原发性头痛在发作开始时表现出昼夜/年节律性，或者直接与睡眠本身有关。偏头痛和丛集性头痛都表现出明显的发作模式，虽然这种发作开始昼夜变化的潜在机制仍有待充分探索，但最近的证据表明存在明显的生理、解剖和遗传趋同。下丘脑已成为偏头痛和丛集性头痛等几种头痛疾病的关键脑区。它参与了稳态调节，包括疼痛处理和睡眠调节，使身体能够对各种刺激做出适当的生理反应。它也是昼夜节律与光同步的关键整合器，部分受垂体腺苷酸环化酶激活肽（PACAP）调节。鉴于该肽在实验性头痛研究中的既定作用，以及其在人类和动物头痛中的广泛研究，仅少数研究调查了其对人类睡眠的影响。鉴于其在昼夜节律同步中的突出作用，已在临床前研究中得到证实，以及外源性 PACAP 能够在实验中引发发作的能力，因此非常有必要进行进一步的研究。目前的综述将重点关注下丘脑在调节睡眠-觉醒和昼夜节律中的作用，并为未来的研究方向提供建议，特别关注 PACAP。
