Evidence map›Paper›PMID 41002104›Full record

Observational studyEuropean journal of neurology2025

PACAP-38 in Cluster Headache: A Prospective, Case-Control Study of a Potential Treatment Target.

Marie-Louise K Søborg, Nunu Lund, Agneta Snoer, Mads Barloese, Rigmor Højland Jensen, Anja Sofie Petersen

Abstract readObservational Study
In one paragraph

Observational study in European journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Observational
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Marie-Louise K SøborgDanish Headache Center, Department of Neurology, University of Copenhagen, Rigshospitalet-Glostrup, Glostrup, Denmark.ORCID 0000-0001-6015-6814
Nunu LundDanish Headache Center, Department of Neurology, University of Copenhagen, Rigshospitalet-Glostrup, Glostrup, Denmark.
Agneta SnoerDanish Headache Center, Department of Neurology, University of Copenhagen, Rigshospitalet-Glostrup, Glostrup, Denmark.
Mads BarloeseDanish Headache Center, Department of Neurology, University of Copenhagen, Rigshospitalet-Glostrup, Glostrup, Denmark.
Rigmor Højland JensenDanish Headache Center, Department of Neurology, University of Copenhagen, Rigshospitalet-Glostrup, Glostrup, Denmark.
Anja Sofie PetersenDanish Headache Center, Department of Neurology, University of Copenhagen, Rigshospitalet-Glostrup, Glostrup, Denmark.ORCID 0000-0002-0125-6038

Funding

H. Lundbeck A/SRegion HovedstadenRigshospitalet
6 · The paper itself

Abstract

backgroundEstimates of pituitary adenylate cyclase-activating peptide-38's (PACAP-38) activity in cluster headache are sparse. We investigated whether plasma levels of PACAP-38 differ between disease states (i.e., bout, remission, chronic) and compared to headache-free controls. Secondly, we assessed a possible correlation between plasma levels of PACAP-38 and Calcitonin gene-related peptide (CGRP).

methodsIn an observational case-control setup, prospectively collected interictal plasma samples from participants in the Danish Cluster Headache Biobank were analyzed for plasma levels of PACAP-38 and CGRP. All participants had blood samples drawn; once if chronic cluster headache or controls, and twice if episodic cluster headache (in bout and in remission phase). Plasma levels were measured with validated immunoassays.

resultsPlasma was derived from 205 patients with cluster headache according to ICHD-3 criteria and 101 sex- and age-matched headache-free controls. PACAP-38 plasma levels were significantly higher in all three disease states of cluster headache: compared to controls, they collectively had a 34.3% (95% CI: 20%-49%, p < 0.0001) higher mean PACAP-38 level. Chronic cluster headache showed the greatest difference by 49.8% (95% CI: 26.7-77.2, p < 0.0001) higher PACAP-38 levels, while episodic cluster headache in bout and remission showed respectively 39.5% (95% CI: 18.8-63.8, p < 0.0001) and 34.1% (95% CI: 14.2-57.5, p = 0.0005) higher plasma levels. No correlation between plasma levels of PACAP-38 and CGRP was demonstrated (Spearmans r = 0.08, p = 0.10).

conclusionsThis large-scale study demonstrated increased PACAP-38 levels in all disease states of cluster headache compared to headache-free controls, strengthening the hope of a possible effect of PACAP-38 targeting treatments in future trials. The lacking correlation between PACAP-38 and CGRP levels should be interpreted with caution and needs to be investigated in future studies.

Indexed as

Cluster HeadachePituitary Adenylate Cyclase-Activating PolypeptideAdultCalcitonin Gene-Related PeptideCase-Control StudiesFemaleHumansMaleMiddle AgedProspective StudiesCalcitonin Gene-Related PeptidePituitary Adenylate Cyclase-Activating Polypeptidecluster headachePACAP38treatment

Identifiers

PMID41002104
PMCPMC12465007

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.