Calcitonin gene-related peptide in migraine: intersection of peripheral inflammation and central modulation

Ann C. Raddant; Andrew F. Russo

doi:10.1017/S1462399411002067

Calcitonin gene-related peptide in migraine: intersection of peripheral inflammation and central modulation

Published online by Cambridge University Press: 29 November 2011

Ann C. Raddant and

Andrew F. Russo

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Ann C. Raddant: Affiliation:
Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA
Andrew F. Russo*: Affiliation:
Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA
*: *Corresponding author: Andrew F. Russo. E-mail: [email protected]

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Abstract

Over the past two decades, a convergence of basic and clinical evidence has established the neuropeptide calcitonin-gene-related peptide (CGRP) as a key player in migraine. Although CGRP is a recognised neuromodulator of nociception, its mechanism of action in migraine remains elusive. In this review, we present evidence that led us to propose that CGRP is well poised to enhance neurotransmission in migraine by both peripheral and central mechanisms. In the periphery, it is thought that local release of CGRP from the nerve endings of meningeal nociceptors following their initial activation by cortical spreading depression is critical for the induction of vasodilation, plasma protein extravasation, neurogenic inflammation and the consequential sensitisation of meningeal nociceptors. Mechanistically, we propose that CGRP release can give rise to a positive-feedback loop involved in localised increased synthesis and release of CGRP from neurons and a CGRP-like peptide called procalcitonin from trigeminal ganglion glia. Within the brain, the wide distribution of CGRP and CGRP receptors provides numerous possible targets for CGRP to act as a neuromodulator.

Type: Review Article
Information: Expert Reviews in Molecular Medicine , Volume 13 , March 2011 , e36

DOI: https://doi.org/10.1017/S1462399411002067 [Opens in a new window]
Copyright: Copyright © Cambridge University Press 2011

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Calcitonin gene-related peptide in migraine: intersection of peripheral inflammation and central modulation

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Calcitonin gene-related peptide in migraine: intersection of peripheral inflammation and central modulation

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