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PACAP27 Triggers Migraine Attacks in Migraine Patients

Pituitary adenylate cyclase-activating polypeptide-27 (PACAP27) triggers migraine attacks without aura in patients with migraine, a new study found. In the crossover study, 20 migraine patients without aura were randomly assigned to receive human PACAP27 or saline infusion over 20 minutes. Migraine and associated symptoms were recorded. Among the findings:

  • All patients completed the study.
  • PACAP27 induced migraine-like attacks in 11 (55%) patients and 2 (10%) developed attacks after placebo.
  • Headache intensity and duration after PACAP27 was significantly greater vs placebo.


Ghanizada H, et al. PACAP27 induces migraine-like attacks in migraine patients. [Published online ahead of print July 12, 2019]. Cephalalgia. doi:10.1177/0333102419864507.


What’s next for migraine treatment? Translational research provided serotonin (5-HT)1B/1D, and, more recently, 1F agonists for acute treatment of migraine. Calcitonin gene-related peptide (CGRP is a transformational target for both acute and preventive treatments, including small molecule CGRP receptor antagonists (gepants) and anti-CGRP and anti-CGRP receptor monoclonal antibodies (MABs). Pituitary adenylate cyclase-activating peptide (PACAP) seems a reasonable next choice, and the current study demonstrates that the isoform PACAP27 can be added to previous trials showing PACAP38 infused in those with migraine trigger migraine-like attacks. PACAP binds to several receptors, but a recent study of an anti-PACAP1 (PAC1) MAB was negative. The questions confronting next steps in migraine translational research include: 1) Would an anti-PACAP ligand (either PACAP38 or PACAP 27) MAB work? 2) Would a different receptor target work? 3) Would a better anti-PAC1 MAB work, that is, was the problem with the molecule tested? 4) Is PACAP even a correct therapeutic target? —Stewart J. Tepper, MD, FAHS, Professor of Neurology, Geisel School of Medicine at Dartmouth, Director, Dartmouth Headache Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH