PACAP38-induced migraine attacks are independent of CGRP signaling: a randomized controlled trial

What Was Tested

The paper reports a study of CGRP (Calcitonin Gene-Related Peptide) and PACAP in the context of migraine, published as a randomized controlled trial.

Calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) are key pathogenic drivers of migraine.

While CGRP has become the target of several mechanism-based therapies, less is known about PACAP38 signaling in migraine pathogenesis.

Who Took Part

The age groups tagged for this paper are young adults, adults and middle-aged adults, both men and women.

In a double-blind, placebo-controlled, parallel-group study, the researchers randomly allocated adults with migraine without aura to receive either an intravenous infusion of 300-mg eptinezumab or matching placebo (isotonic saline) over 30 min.

How the Study Was Run

The researchers set it up as a randomized, double-blind, placebo-controlled and parallel-group study.

Random assignment meant chance, not the researchers, decided who got CGRP (Calcitonin Gene-Related Peptide) and who got the comparison, which limits bias.

Blinding on both sides kept the participants and researchers unaware of who received CGRP (Calcitonin Gene-Related Peptide).

A placebo (an inactive look-alike) gave the CGRP (Calcitonin Gene-Related Peptide) group a baseline to be compared against.

Groups ran in parallel: each of the participants stayed in one arm throughout.

The primary endpoint was the incidence of migraine attacks during the 24-hour observational period post-infusion of eptinezumab or placebo.

Key secondary endpoints included between-group differences in incidence of headache, and area under the curve (AUC) for headache intensity scores, diameter of the superficial temporal artery (STA) and facial skin blood flow.

What Was Measured

Topics PubMed links to this paper include Pituitary Adenylate Cyclase-Activating Polypeptide, Calcitonin Gene-Related Peptide, Antibodies, Monoclonal, Humanized, Migraine Disorders and Signal Transduction.

Author keywords: CGRP, Drug targets, Headache, PACAP-38, Pain and Pathophysiology.

What This Means in Plain Language

The paper is a randomized, double-blind and placebo-controlled study of CGRP (Calcitonin Gene-Related Peptide) and PACAP in people with migraine.

Its findings take up roughly 8 sentences of the abstract and are left out here on purpose; the source paper is the place to read them.

The publication is from 2025 (The journal of headache and pain), a journal based in England.

More context: the CGRP (Calcitonin Gene-Related Peptide) compound page and the PACAP compound page, Migraine research.