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Shared and independent roles of CGRP and PACAP in migraine pathophysiology
Journal article   Open access   Peer reviewed

Shared and independent roles of CGRP and PACAP in migraine pathophysiology

Adisa Kuburas and Andrew F. Russo
Journal of headache and pain, Vol.24(1), 34
04/03/2023
DOI: 10.1186/s10194-023-01569-2
PMCID: PMC10069045
PMID: 37009867
url
https://doi.org/10.1186/s10194-023-01569-2View
Published (Version of record) Open Access

Abstract

The neuropeptides calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) have emerged as mediators of migraine pathogenesis. Both are vasodilatory peptides that can cause migraine-like attacks when infused into people and migraine-like symptoms when injected into rodents. In this narrative review, we compare the similarities and differences between the peptides in both their clinical and preclinical migraine actions. A notable clinical difference is that PACAP, but not CGRP, causes premonitory-like symptoms in patients. Both peptides are found in distinct, but overlapping areas relevant to migraine, most notably with the prevalence of CGRP in trigeminal ganglia and PACAP in sphenopalatine ganglia. In rodents, the two peptides share activities, including vasodilation, neurogenic inflammation, and nociception. Most strikingly, CGRP and PACAP cause similar migraine-like symptoms in rodents that are manifested as light aversion and tactile allodynia. Yet, the peptides appear to act by independent mechanisms possibly by distinct intracellular signaling pathways. The complexity of these signaling pathways is magnified by the existence of multiple CGRP and PACAP receptors that may contribute to migraine pathogenesis. Based on these differences, we suggest PACAP and its receptors provide a rich set of targets to complement and augment the current CGRP-based migraine therapeutics.
Receptors CGRP Intracellular signaling Migraine PACAP Review

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