Journal
CEPHALALGIA
Volume 39, Issue 3, Pages 390-402Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/0333102418756863
Keywords
Migraine; brainstem; CGRP
Categories
Funding
- Medical Research Council [MR/P006264/1]
- MRC [MR/P006264/1] Funding Source: UKRI
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Background Migraine is a severe debilitating disorder of the brain that is ranked as the sixth most disabling disorder globally, with respect to disability adjusted life years, and there remains a significant unmet demand for an improved understanding of its underlying mechanisms. In conjunction with perturbed sensory processing, migraine sufferers often present with diverse neurological manifestations (premonitory symptoms) that highlight potential brainstem involvement. Thus, as the field moves away from the view of migraine as a consequence of purely vasodilation to a greater understanding of migraine as a complex brain disorder, it is critical to consider the underlying physiology and pharmacology of key neural networks likely involved. Discussion The current review will therefore focus on the available evidence for the brainstem as a key regulator of migraine biology and associated symptoms. We will further discuss the potential role of CGRP in the brainstem and its modulation for migraine therapy, given the emergence of targeted CGRP small molecule and monoclonal antibody therapies. Conclusion The brainstem forms a functional unit with several hypothalamic nuclei that are capable of modulating diverse functions including migraine-relevant trigeminal pain processing, appetite and arousal regulatory networks. As such, the brainstem has emerged as a key regulator of migraine and is appropriately considered as a potential therapeutic target. While currently available CGRP targeted therapies have limited blood brain barrier penetrability, the expression of CGRP and its receptors in several key brainstem nuclei and the demonstration of brainstem effects of CGRP modulation highlight the significant potential for the development of CNS penetrant molecules.
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