title: Part II: Biochemical changes after pituitary adenylate cyclase-activating polypeptide-38 infusion in migraine patients.
abstract: 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.
authors.affiliation: 1 Danish Headache Center and Department of Neurology, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Song
authors.initials: S
authors.lastname: Guo
authors.affiliation: 1 Danish Headache Center and Department of Neurology, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anne Luise Haulund
authors.initials: AL
authors.lastname: Vollesen
authors.affiliation: 2 Department of Clinical Biochemistry, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Young Bae Lee
authors.initials: YB
authors.lastname: Hansen
authors.affiliation: 3 Department of Diagnostics, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Erik
authors.initials: E
authors.lastname: Frandsen
authors.affiliation: 4 Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Gentofte, Denmark.
authors.forename: Malene Rohr
authors.initials: MR
authors.lastname: Andersen
authors.affiliation: 1 Danish Headache Center and Department of Neurology, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Faisal Mohammad
authors.initials: FM
authors.lastname: Amin
authors.affiliation: 5 Department of Clinical Biochemistry, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Fahrenkrug
authors.affiliation: 1 Danish Headache Center and Department of Neurology, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jes
authors.initials: J
authors.lastname: Olesen
authors.affiliation: 1 Danish Headache Center and Department of Neurology, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Messoud
authors.initials: M
authors.lastname: Ashina
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000097:blood* / Q000139:chemically induced* / Q000175:diagnosis; D009479:Neuropeptides / Q000097:blood; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000008:administration & dosage* / Q000009:adverse effects*; D011795:Surveys and Questionnaires; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014409:Tumor Necrosis Factor-alpha
keywords: Migraine; calcitonin gene-related peptide; mast cells; pituitary adenylate cyclase-activating polypeptide-38; pituitary hormones; vasoactive intestinal polypeptide