Headache Group, Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
International Medical College, King Mongkut's Institute of Technology Ladkrabang, Bangkok, Thailand.
Neurotherapeutics. 2018 Apr;15(2):377-390. doi: 10.1007/s13311-017-0602-3.
The hypothalamus is involved in the regulation of homeostatic mechanisms and migraine-related trigeminal nociception and as such has been hypothesized to play a central role in the migraine syndrome from the earliest stages of the attack. The hypothalamus hosts many key neuropeptide systems that have been postulated to play a role in this pathophysiology. Such neuropeptides include but are not exclusive too orexins, oxytocin, neuropeptide Y, and pituitary adenylate cyclase activating protein, which will be the focus of this review. Each of these peptides has its own unique physiological role and as such many preclinical studies have been conducted targeting these peptide systems with evidence supporting their role in migraine pathophysiology. Preclinical studies have also begun to explore potential therapeutic compounds targeting these systems with some success in all cases. Clinical efficacy of dual orexin receptor antagonists and intranasal oxytocin have been tested; however, both have yet to demonstrate clinical effect. Despite this, there were limitations in these cases and strong arguments can be made for the further development of intranasal oxytocin for migraine prophylaxis. Regarding neuropeptide Y, work has yet to begun in a clinical setting, and clinical trials for pituitary adenylate cyclase activating protein are just beginning to be established with much optimism. Regardless, it is becoming increasingly clear the prominent role that the hypothalamus and its peptide systems have in migraine pathophysiology. Much work is required to better understand this system and the early stages of the attack to develop more targeted and effective therapies aimed at reducing attack susceptibility with the potential to prevent the attack all together.
下丘脑参与调节体内平衡机制和偏头痛相关的三叉神经痛觉，因此被认为在偏头痛综合征的早期阶段就发挥了核心作用。下丘脑拥有许多关键的神经肽系统，这些系统被认为在这种病理生理学中发挥作用。这些神经肽包括但不限于食欲素、催产素、神经肽 Y 和垂体腺苷酸环化酶激活蛋白，这将是本综述的重点。这些肽中的每一种都有其独特的生理作用，因此许多针对这些肽系统的临床前研究已经进行，有证据支持它们在偏头痛病理生理学中的作用。临床前研究也开始探索针对这些系统的潜在治疗化合物，在所有情况下都取得了一定的成功。双重食欲素受体拮抗剂和鼻内催产素的临床疗效已得到测试；然而，两者都尚未显示出临床效果。尽管如此，在这些情况下存在局限性，并且可以强有力地支持进一步开发鼻内催产素用于偏头痛预防。关于神经肽 Y，其在临床环境中的工作尚未开始，而垂体腺苷酸环化酶激活蛋白的临床试验才刚刚开始，人们对此充满乐观。无论如何，越来越明显的是，下丘脑及其肽系统在偏头痛病理生理学中起着重要作用。需要做更多的工作来更好地理解这个系统和偏头痛发作的早期阶段，以开发更有针对性和更有效的治疗方法，旨在降低发作的易感性，并有可能完全预防发作。
