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Biochemical Modulation and Pathophysiology of Migraine

Chan, Calvin BBMedSc, MBChB; Wei, Diana Y. BSc, MBBS; Goadsby, Peter J. MD, PhD

Section Editor(s): Digre, Kathleen B. MD; Friedman, Deborah I. MD, MPH

doi: 10.1097/WNO.0000000000000875
Disease of the Year: Migraine

Background: Migraine is a common disabling neurological disorder where attacks have been recognized to consist of more than headache. The premonitory, headache, and postdromal phases are the various phases of the migraine cycle, where aura can occur before, during, or after the onset of pain. Migraine is also associated with photosensitivity and cranial autonomic symptoms, which includes lacrimation, conjunctival injection, periorbital edema, ptosis, nasal congestion, and rhinorrhoea. This review will present the current understanding of migraine pathophysiology and the relationship to the observed symptoms.

Evidence Acquisition: The literature was reviewed with specific focus on clinical, neurophysiological, functional imaging, and preclinical studies in migraine including the studies on the role of calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase activating polypeptide (PACAP).

Results: The phases of the migraine cycle have been delineated by several studies. The observations of clinical symptoms help develop hypotheses of the key structures involved and the biochemical and neuronal pathways through which the effects are mediated. Preclinical studies and functional imaging studies have provided evidence for the role of multiple cortical areas, the diencephalon, especially the hypothalamus, and certain brainstem nuclei in the modulation of nociceptive processing, symptoms of the premonitory phase, aura, and photophobia. CGRP and PACAP have been found to be involved in nociceptive modulation and through exploration of CGRP mechanisms, new successful treatments have been developed.

Conclusions: Migraine is a complex neural disorder and is important to understand when seeing patients who present to neuro-ophthalmology, especially with the successful translation from preclinical and clinical research leading to successful advances in migraine management.

Headache Group, Department of Basic and Clinical Neuroscience (CC, DYW, PJG), Institute of Psychology, Psychiatry and Neuroscience, King's College London, London, United Kingdom; and NIHR-Wellcome Trust King's Clinical Research Facility (CC, DYW, PJG), SLaM Biomedical Research Centre, King's College Hospital, London, United Kingdom.

Address correspondence to Peter J. Goadsby, MD, PhD, Wellcome Foundation Building, King's College Hospital, London SE5 9PJ, United Kingdom; E-mail:

P. J. Goadsby reports grants and personal fees from Amgen and Eli-Lilly and Company, and personal fees from Alder Biopharmaceuticals, Allergan, Autonomic Technologies Inc, Biohaven Pharmaceuticals Inc, Dr Reddy's Laboratories, Electrocore LLC, eNeura, Impel Neuropharma, MundiPharma, Novartis, Teva Pharmaceuticals, Trigemina Inc, and WL Gore, and personal fees from MedicoLegal work, Massachusetts Medical Society, Up-to-Date, Oxford University Press, and Wolters Kluwer, and a patent magnetic stimulation for headache assigned to eNeura without fee. This paper represents independent research funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care.

© 2019 by North American Neuro-Ophthalmology Society