New research shows CGRP monoclonal antibody treatment may not prevent migraine attacks triggered by the neuropeptide PACAP-38. This study suggests PACAP-38 may act through a different pathway and could become a future preventive option for people who don’t respond to CGRP-based treatments. Molly O’Brien explains in this Migraine Minute News Update. 

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Images courtesy: Springer Nature. The Journal of Headache and Pain. doi: 10.1186/s10194-025-02022-2
Creative Commons license: https://creativecommons.org/licenses/by-nc-nd/4.0/

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Does PACAP 38 Work Differently Than CGRP?

A new study published in the Journal of Headache and Pain found that migraine attacks can be triggered by the neuropeptide PACAP-38 despite pre-treatment with a CGRP monoclonal antibody.

Researchers gave 38 participants with migraine an infusion of eptinezumab—a CGRP monoclonal antibody—or placebo, followed by PACAP-38. The results showed no difference in the incidence of migraine attacks between the two groups.

This study suggests that PACAP-38 may trigger migraine attacks through a different pathway than CGRP. Treatments targeting PACAP-38 may offer a new preventive option for people who’ve had limited or no success with CGRP monoclonal antibodies.