Headache Group, NIHR King's Clinical Research Facility and SLaM Biomedical Research Centre, The Wolfson Sensory, Pain and Regeneration Research Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9PJ, UK.
Department of Neurology, University of California, Los Angeles, USA.
J Headache Pain. 2023 Aug 11;24(1):106. doi: 10.1186/s10194-023-01617-x.
The premonitory phase, or prodrome, of migraine, provides valuable opportunities to study attack initiation and for treating the attack before headache starts. Much that has been learned about this phase in recent times has come from the outcomes of functional imaging studies. This review will summarise these studies to date and use their results to provide some feasible insights into migraine neurobiology.
The ability to scan repeatedly a patient without radiation and with non-invasive imaging modalities, as well as the recognition that human experimental migraine provocation compounds, such as nitroglycerin (NTG) and pituitary adenylate cyclase activating polypeptide (PACAP), can trigger typical premonitory symptoms (PS) and migraine-like headache in patients with migraine, have allowed feasible and reproducible imaging of the premonitory phase using NTG. Some studies have used serial scanning of patients with migraine to image the migraine cycle, including the 'pre-ictal' phase, defined by timing to headache onset rather than symptom phenotype. Direct observation and functional neuroimaging of triggered PS have also revealed compatible neural substrates for PS in the absence of headache. Various imaging methods including resting state functional MRI (rsfMRI), arterial spin labelling (ASL), positron emission tomography (PET) and diffusion tensor imaging (DTI) have been used. The results of imaging the spontaneous and triggered premonitory phase have been largely consistent and support a theory of central migraine attack initiation involving brain areas such as the hypothalamus, midbrain and limbic system. Early dysfunctional pain, sensory, limbic and homeostatic processing via monoaminergic and peptidergic neurotransmission likely manifests in the heterogeneous PS phenotype.
Advances in human migraine research, including the use of functional imaging techniques lacking radiation or radio-isotope exposure, have led to an exciting opportunity to study the premonitory phase using repeated measures imaging designs. These studies have provided novel insights into attack initiation, migraine neurochemistry and therapeutic targets. Emerging migraine-specific therapies, such as those targeting calcitonin gene-related peptide (CGRP), are showing promise acutely when taken during premonitory phase to reduce symptoms and prevent subsequent headache. Therapeutic research in this area using PS for headache onset prediction and early treatment is likely to grow in the future.
偏头痛的前驱期或先兆期为研究发作起始提供了有价值的机会，并且可以在头痛发作之前进行治疗。近年来，许多关于这一阶段的认识都来自功能影像学研究的结果。本综述将总结迄今为止的这些研究，并利用其结果为偏头痛神经生物学提供一些可行的见解。
能够对患者进行重复无辐射的非侵入性成像，以及认识到人类实验性偏头痛诱发化合物，如硝化甘油（NTG）和垂体腺苷酸环化酶激活肽（PACAP），可以在偏头痛患者中引发典型的前驱症状（PS）和偏头痛样头痛，使得使用 NTG 对前驱期进行可行且可重复的成像成为可能。一些研究使用偏头痛患者的连续扫描来对偏头痛周期进行成像，包括由头痛发作时间而不是症状表型定义的“发作前”阶段。对触发的前驱症状的直接观察和功能神经影像学研究也揭示了在没有头痛的情况下前驱症状的相容的神经基础。各种成像方法，包括静息态功能磁共振成像（rsfMRI）、动脉自旋标记（ASL）、正电子发射断层扫描（PET）和弥散张量成像（DTI）已经被使用。自发和触发前驱期的成像结果基本一致，支持了涉及下丘脑、中脑和边缘系统等脑区的中枢偏头痛发作起始理论。早期的功能障碍性疼痛、感觉、边缘和通过单胺能和肽能神经递质传递的内稳态处理可能表现为异质的前驱症状表型。
包括使用缺乏辐射或放射性同位素暴露的功能成像技术在内的人类偏头痛研究的进展，为使用重复测量成像设计研究前驱期提供了一个令人兴奋的机会。这些研究为发作起始、偏头痛神经化学和治疗靶点提供了新的见解。新兴的偏头痛特异性治疗方法，如靶向降钙素基因相关肽（CGRP）的治疗方法，在先兆期开始时使用时显示出在减轻症状和预防随后头痛方面的疗效。未来，针对先兆期进行头痛发作预测和早期治疗的该领域的治疗研究可能会增加。
