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October 01, 2013; 81 (14) Editorial

Is CGRP a marker for chronic migraine?

Stephen D. Silberstein, Lars Edvinsson
First published August 23, 2013, DOI: https://doi.org/10.1212/WNL.0b013e3182a6cc33
Stephen D. Silberstein
From the Jefferson Headache Center (S.D.S.), Jefferson Hospital for Neuroscience, Philadelphia, PA; and Internal Medicine (L.E.), Lund University, Sweden.
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Lars Edvinsson
From the Jefferson Headache Center (S.D.S.), Jefferson Hospital for Neuroscience, Philadelphia, PA; and Internal Medicine (L.E.), Lund University, Sweden.
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Is CGRP a marker for chronic migraine?
Stephen D. Silberstein, Lars Edvinsson
Neurology Oct 2013, 81 (14) 1184-1185; DOI: 10.1212/WNL.0b013e3182a6cc33

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Calcitonin gene-related peptide (CGRP) research was initiated by Poyner et al.,1 who found that the calcitonin gene encodes the 37–amino acid neuropeptide CGRP in neuronal tissue. Within months, the Lund group produced antibodies toward α-CGRP and developed sensitive methods to study the role of this peptide in the cranial circulation. Intracranial vessels and the trigeminal ganglion harbor this potent vasodilator peptide.2 Functionally, CGRP has a substantial role in the trigeminovascular reflex.3 The calcitonin family is now well-characterized and contains 6 members: calcitonin, amylin, adenomedullin-2, adrenomedullin, and CGRP (2 isoforms: α-CGRP and β-CGRP).4 The α- and β-isoforms of CGRP are similar in their biological activities but show different tissue distributions. β-CGRP is mainly found in enteric nerves and in the pituitary gland, while α-CGRP is found predominantly in sensory neurons and in the CNS.5 CGRP causes cranial vasodilatation and facilitates nociception. During a migraine attack, trigeminal activation results in the release of CGRP from presynaptic nerve terminals and induces vasodilatation and neurogenic inflammation in leptomeningeal and extracranial vessels, which gives rise to the typical throbbing pain of migraine. Goadsby and Edvinsson6 showed that plasma concentrations of CGRP are elevated in the external jugular venous blood during migraine headaches and that sumatriptan can abort the rise in CGRP and the headache.4 CGRP given IV causes headache only in migraine patients and CGRP antagonists are effective for the acute treatment of migraine.7 Until now, CGRP elevation in the plasma has not been reproduced in all studies.8 However, technical problems have sometimes hampered the proper measurements of CGRP.9

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