TY - JOUR

T1 - PACAP38 dose-response pilot study in migraine patients

AU - Vollesen, Anne Luise Haulund

AU - Guo, Song

AU - Ashina, Messoud

PY - 2017/4/15

Y1 - 2017/4/15

N2 - 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.

AB - 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.

KW - Adult

KW - Cross-Over Studies

KW - Dose-Response Relationship, Drug

KW - Double-Blind Method

KW - Female

KW - Humans

KW - Infusions, Intravenous

KW - Male

KW - Middle Aged

KW - Migraine without Aura

KW - Pilot Projects

KW - Pituitary Adenylate Cyclase-Activating Polypeptide

KW - Vasodilator Agents

KW - Young Adult

KW - Journal Article

KW - Randomized Controlled Trial

U2 - 10.1177/0333102416644435

DO - 10.1177/0333102416644435

M3 - Journal article

C2 - 27084887

VL - 37

SP - 391

EP - 395

JO - Cephalalgia

JF - Cephalalgia

SN - 0800-1952

IS - 4

ER -