Part II: Biochemical changes after pituitary adenylate cyclase-activating polypeptide-38 infusion in migraine patients

• Published in: Cephalalgia Vol. 37; no. 2; pp. 136 - 147
• Main Authors: Guo, Song, Vollesen, Anne Luise Haulund, Hansen, Young Bae Lee, Frandsen, Erik, Andersen, Malene Rohr, Amin, Faisal Mohammad, Fahrenkrug, Jan, Olesen, Jes, Ashina, Messoud
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.02.2017
• Subjects: Adult; Cohort Studies; Denmark - epidemiology; Double-Blind Method; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Migraine Disorders - blood; Migraine Disorders - chemically induced; Migraine Disorders - diagnosis; Neuropeptides - blood; Pituitary Adenylate Cyclase-Activating Polypeptide - administration & dosage; Pituitary Adenylate Cyclase-Activating Polypeptide - adverse effects; Surveys and Questionnaires; Tumor Necrosis Factor-alpha - blood; calcitonin gene-related peptide; mast cells; pituitary adenylate cyclase-activating polypeptide-38; Migraine; vasoactive intestinal polypeptide; pituitary hormones
• ISSN: 0333-1024; 1468-2982
• DOI: 10.1177/0333102416639517

Background Intravenous infusion of pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) provokes migraine attacks in 65–70% of migraine without aura (MO) patients. We investigated whether PACAP38 infusion causes changes in the endogenous production of PACAP38, vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), tumour necrosis factor alpha (TNFα), S100 calcium binding protein B (S100B), neuron-specific enolase and pituitary hormones in migraine patients. Methods We allocated 32 previously genotyped MO patients to receive intravenous infusion PACAP38 (10 pmol/kg/minute) for 20 minutes and recorded migraine-like attacks. Sixteen of the patients were carriers of the risk allele rs2274316 (MEF2D), which confers increased risk of MO and may regulate PACAP38 expression, and 16 were non-carriers. We collected blood samples at baseline and 20, 30, 40, 60 and 90 minutes after the start of the infusion. A control group of six healthy volunteers received intravenous saline. Results PACAP38 infusion caused significant changes in plasma concentrations of VIP (p = 0.026), prolactin (p = 0.011), S100B (p < 0.001) and thyroid-stimulating hormone (TSH; p = 0.015), but not CGRP (p = 0.642) and TNFα (p = 0.535). We found no difference in measured biochemical variables after PACAP38 infusion in patients who later developed migraine-like attacks compared to those who did not (p > 0.05). There was no difference in the changes of biochemical variables between patients with and without the MEF2D-associated gene variant (p > 0.05). Conclusion PACAP38 infusion elevated the plasma levels of VIP, prolactin, S100B and TSH, but not CGRP and TNFα. Development of delayed migraine-like attacks or the presence of the MEF2D gene variant was not associated with pre-ictal changes in plasma levels of neuropeptides, TNFα and pituitary hormones.