CGRP and its receptors provide new insights into migraine pathophysiology

Abstract

Over the past 300 years, the migraine field has been dominated by two main theories—the vascular theory and the central neuronal theory. The success of vasoconstrictors such as ergotamine and the triptans in treating acute migraine bolstered the vascular theory, but evidence is now emerging that vasodilatation is neither necessary nor sufficient to induce a migraine attack. Attention is now turning to the core migraine circuits in the brain, which include the trigeminal ganglia, trigeminal nucleus, medullary modulatory regions, pons, periaqueductal gray matter, hypothalamus and thalamus. Migraine triggers are likely to reflect a disturbance in overall balance of the circuits involved in the modulation of sensory activity, particularly those with relevance to the head. In this Review, we consider the evidence pointing towards a neuronal mechanism in migraine development, highlighting the role of calcitonin gene-related peptide (CGRP), which is found in small to medium-sized neurons in the trigeminal ganglion. CGRP is released during migraine attacks and can trigger migraine in patients, and CGRP receptor antagonists can abort migraine. We also examine whether other drugs, such as triptans, might exert their antimigraine effects via their actions on the neuronal circuit as opposed to the intracranial vasculature.

Key Points

  • Migraine pathophysiology involves complex peripheral and central processes

  • Neither vasodilatation nor neurogenic inflammation alone is sufficient to explain migraine pathophysiology

  • The brains of patients with migraine are susceptible to activation by various triggers that do not affect non-migraineurs

  • The sensitivity of migraineurs to specific triggers possibly has a genetic basis

  • Calcitonin gene-related peptide seems to have a central role in migraine pathogenesis through both peripheral and central mechanisms

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Figure 1: Migraine as a deficit in filtering of sensory inputs—a model.

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T. W. Ho, L. Edvinsson and P. J. Goadsby contributed equally to researching data for the article, discussion of content, writing, and reviewing and/or editing of the manuscript before submission.

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Correspondence to Lars Edvinsson.

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T. W. Ho is a Director at Merck Sharp & Dohme. The other authors declare no competing interests.

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Ho, T., Edvinsson, L. & Goadsby, P. CGRP and its receptors provide new insights into migraine pathophysiology. Nat Rev Neurol 6, 573–582 (2010). https://doi.org/10.1038/nrneurol.2010.127

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