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

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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.

Original languageEnglish
JournalCephalalgia : an international journal of headache
Issue number2
Pages (from-to)136-147
Publication statusPublished - 1 Feb 2017

ID: 49697391