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Review
. 2017 Nov 23;18(1):110.
doi: 10.1186/s10194-017-0821-3.

PACAP38 in human models of primary headaches

Håkan Ashina  1 , Song Guo  1 , Anne L H Vollesen  1 , Messoud Ashina  2
Affiliations
Review

PACAP38 in human models of primary headaches

Håkan Ashina et al. J Headache Pain. .

Abstract

Background: To review the role of PACAP38 in human models of primary headaches, discuss possible mechanisms of PACAP38-induced migraine, and outline future directions.

Discussion: Experimental studies have established PACAP38 as a potent pharmacological "trigger" molecule of migraine-like attacks. These studies have also revealed a heterogeneous PACAP38 migraine response in migraine without aura patients. In addition, findings from brain imaging studies have demonstrated neuronal and vascular changes in migraine patients both ictally and interictally after PACAP38 infusion.

Conclusion: Human migraine models have shed light on the importance of PACAP38 in the pathophysiology of primary headaches. These studies have also pointed to the PAC1 receptor and the PACAP38 molecule itself as target sites for drug testing. Future research should seek to understand the mechanisms underlying PACAP38-induced migraine. The results from an ongoing proof of concept randomized clinical trial may reveal the therapeutic potential of anti-PAC1 receptor antibodies for migraine prevention.

Keywords: Human provocation models; Migraine; PAC1; PACAP38; Primary headaches.

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Conflict of interest statement

Ethics approval and consent to participate

Not applicable

Consent for publication

Not applicable

Competing interests

Messoud Ashina is a consultant, speaker or scientific advisor for Allergan, Amgen, Alder, ATI, Eli Lilly, Novartis, and Teva, primary investigator for Amgen 20,120,178 (Phase 2), 20,120,295 (Phase 2), 20,130,255 (OLE), 20,120,297 (Phase 3), Alder ALD403-CLIN-001 (Phase 3), Amgen PAC1 20,150,308 (Phase 2a), and GM-11 gamma-Core-R trials, and reports grants from Lundbeck Foundation (R155–2014-171). Håkan Ashina, Song Guo, and Anne Luise Haulund Vollesen have no conflicts of interest.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Proportion (median and range) of patients who developed migraine-like attacks and of patients who did not develop migraine-like attacks after PACAP38 infusion [29, 34, 54]
See this image and copyright information in PMC

References

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