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

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 T-0, T-20, T-30, and T-90. 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.

Automated summary

In this study, the researchers investigated the effects of PACAP and VIP on plasma levels of VIP and their contribution to induced cluster headache attacks. The results showed a significant increase in plasma VIP levels during PACAP infusion in individuals with episodic cluster headache, but not in those with chronic cluster headache. Further studies are needed to understand the role of VIP and the parasympathetic system in cluster headache.