Plasma levels of VIP are not elevated during PACAP- and VIP-induced cluster headache attacks: an exploratory study

Christina Deligianni; Lanfranco Pellesi; Basit Ali Chaudhry; Anne Luise Haulund Vollesen; Agneta Henriette Snoer; Jens Hannibal; Rigmor Højland Jensen; Messoud Ashina

doi:10.3389/fneur.2023.1135246

Plasma levels of VIP are not elevated during PACAP- and VIP-induced cluster headache attacks: an exploratory study

Front Neurol. 2023 Apr 18:14:1135246. doi: 10.3389/fneur.2023.1135246. eCollection 2023.

Authors

Christina Deligianni¹, Lanfranco Pellesi¹, Basit Ali Chaudhry¹, Anne Luise Haulund Vollesen¹, Agneta Henriette Snoer¹, Jens Hannibal², Rigmor Højland Jensen¹, Messoud Ashina¹

Affiliations

¹ Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
² Department of Clinical Biochemistry, Bispebjerg Frederiksberg Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.

Abstract

Background: Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) provoked cluster headache attacks in individuals with episodic cluster headache during their active phase and individuals with chronic cluster headache. In this study, we investigated whether infusions of PACAP and VIP caused alterations in plasma levels of VIP and their potential contribution to induced cluster headache attacks.

Methods: Participants received either PACAP or VIP infusion for 20 min on 2 separate days with an interval of at least 7 days in between. Blood collection was performed at T₀, T₂₀, T₃₀, and T₉₀. Plasma levels of VIP were measured using a validated radioimmunoassay method.

Results: Blood samples were collected from participants with episodic cluster headache in the active phase (eCHA, n = 14), remission (eCHR, n = 15), and from participants with chronic cluster headache (cCH, n = 15). Baseline levels of VIP did not differ among the three groups (p = 0.1161). During PACAP infusion, mixed-effects analysis revealed a significant increase in plasma levels of VIP in eCHA (p = 0.0300) and eCHR (p = 0.0058) but not in cCH (p = 0.2930). We found no difference in the increase of plasma VIP levels between patients who developed PACAP38- or VIP-induced attacks.

Conclusion: Cluster headache attacks induced by PACAP38 or VIP infusion are not associated with changes in plasma levels of VIP. Further studies are needed to investigate the role of VIP and the parasympathetic system in cluster headache.

Clinical trial registration: The parent study is registered at ClinicalTrials.gov (NCT03814226).

Keywords: PACAP38; VIP; cluster headache; headache; migraine; pain; parasympathetic system.

Associated data

ClinicalTrials.gov/NCT03814226

Grants and funding

The study was funded by grants from Lundbeckfonden (grant R252-2017-1317) and the Research Foundation of Rigshospitalet. CD was supported by an IHS research fellowship grant. MA was supported by the Lundbeck Foundation Professor Grant (R310-2018–3711). Funding sources had no influence on study design, patient inclusion, or data interpretation. JH is supported by the Danish Biotechnology Center for Cellular Communication.