title: PACAP38 dose-response pilot study in migraine patients.
abstract: Background Intravenous infusion of 10 pmol/kg/min pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) induces migraine-like attacks in migraine patients without aura (MO). Here, we conducted a pilot study and investigated if lower doses of PACAP38 exert similar migraine-inducing abilities. Methods We randomly allocated six MO patients to receive intravenous infusion of 4, 6, and 8 pmol/kg/min of PACAP38 over 20 minutes in a double-blind, three-way cross-over study. Headache and migraine characteristics were recorded during hospital (0-2 hours) and post-hospital (2-13 hours) phases. Results PACAP38 induced migraine-like attacks in one out of six patients with 4 pmol, two out of six patients with 6 pmol and three out of six patients with 8 pmol ( p = 0.368). All patients reported head pain after 8 pmol/kg/min, whereas five of six participants reported head pain after both 4 and 6 pmol/kg/min. We found no difference between the three doses in the AUC for headache intensity over the 12-hour observation period ( p = 0.142). An exploratory analysis showed a significant difference between 4 pmol and 8 pmol ( p = 0.031). Conclusion A trend of a dose-response relationship between dose of PACAP38 and incidence of migraine was observed. We suggest that 10 pmol/kg/min PACAP38 is the most optimal dose to induce migraine-like attacks.
authors.affiliation: Danish Headache Center and Department of Neurology, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Anne Luise Haulund
authors.initials: AL
authors.lastname: Vollesen
authors.affiliation: Danish Headache Center and Department of Neurology, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Song
authors.initials: S
authors.lastname: Guo
authors.affiliation: Danish Headache Center and Department of Neurology, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Messoud
authors.initials: M
authors.lastname: Ashina
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D020326:Migraine without Aura / Q000139:chemically induced*; D010865:Pilot Projects; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000008:administration & dosage* / Q000009:adverse effects*; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014665:Vasodilator Agents
keywords: Migraine; dose-response; experimental migraine model; headache; pituitary adenylate cyclase-activating polypeptide-38