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Updated: Feb 11, 2026

Modeling Neural Immune Signaling of Episodic and Chronic Migraine Using Spreading Depression In Vitro
Published on: June 13, 2011
Cortical spreading depression as a site of origin for migraine: Role of CGRP
Liesl N Close1, Sajedeh Eftekhari2, Minyan Wang3
11 Department of Neurosurgery, University of Iowa, Iowa City, IA, USA.
Premise:
Migraine is a complex neurologic disorder that leads to significant disability, yet remains poorly understood.
Problem:
One potential triggering mechanism in migraine with aura is cortical spreading depression, which can activate the trigeminal nociceptive system both peripherally and centrally in animal models. A primary neuropeptide of the trigeminal system is calcitonin gene-related peptide, which is a potent vasodilatory peptide and is currently a major therapeutic target for migraine treatment. Despite the importance of both cortical spreading depression and calcitonin gene-related peptide in migraine, the relationship between these two players has been relatively unexplored. However, recent data suggest several potential vascular and neural connections between calcitonin gene-related peptide and cortical spreading depression.
Conclusion:
This review will outline calcitonin gene-related peptide-cortical spreading depression connections and propose a model in which cortical spreading depression and calcitonin gene-related peptide act at the intersection of the vasculature and cortical neurons, and thus contribute to migraine pathophysiology.
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