Department of Neurosurgery, University of Texas Health Science Center at Houston, Houston, Texas.
Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston, Houston, Texas.
Acta Physiol (Oxf). 2019 Jan;225(1):e13161. doi: 10.1111/apha.13161. Epub 2018 Jul 25.
Circadian rhythms of physiology are the keys to health and fitness, as dysregulation, by genetic mutations or environmental factors, increases disease risk and aggravates progression. Molecular and physiological studies have shed important light on an intrinsic clock that drives circadian rhythms and serves essential roles in metabolic homoeostasis, organ physiology and brain functions. One exciting new area in circadian research is pain, including headache and neuropathic pain for which new mechanistic insights have recently emerged. For example, cluster headache is an intermittent pain disorder with an exceedingly precise circadian timing, and preliminary evidence is emerging linking several circadian components (eg, Clock and Nr1d1) with the disease. In this review, we first discuss the broad metabolic and physiological relevance of the circadian timing system. We then provide a detailed review of the circadian relevance in pain disease and physiology, including cluster headache, migraine, hypnic headache and neuropathic pain. Finally, we describe potential therapeutic implications, including existing pain medicines and novel clock-modulating compounds. The physiological basis for the circadian rhythms in pain is an exciting new area of research with profound basic and translational impact.
生理的昼夜节律是健康和健身的关键，因为遗传突变或环境因素引起的失调会增加疾病风险并加重病情进展。分子和生理学研究揭示了内在生物钟，它驱动昼夜节律，并在代谢稳态、器官生理学和大脑功能中发挥重要作用。昼夜节律研究的一个令人兴奋的新领域是疼痛，包括头痛和神经性疼痛，最近出现了新的机制见解。例如，丛集性头痛是一种间歇性疼痛障碍，具有极其精确的昼夜节律，初步证据表明几种昼夜节律成分（例如 Clock 和 Nr1d1）与该疾病有关。在这篇综述中，我们首先讨论了昼夜计时系统的广泛代谢和生理相关性。然后，我们详细回顾了疼痛疾病和生理学中的昼夜节律相关性，包括丛集性头痛、偏头痛、催眠性头痛和神经性疼痛。最后，我们描述了潜在的治疗意义，包括现有的疼痛药物和新型时钟调节化合物。疼痛昼夜节律的生理基础是一个令人兴奋的新研究领域，具有深远的基础和转化影响。
