PACAP vs. CGRP in Migraine: Comparing Two Key Neuropeptide Targets
PACAP emerges as a complementary migraine target to CGRP, with distinct roles in autonomic symptoms and potentially different patient populations.
Quick Facts
What This Study Found
CGRP and PACAP play complementary but distinct roles in migraine — CGRP drives trigeminal pain while PACAP primarily influences autonomic symptoms.
Key Numbers
Both peptides elevate cAMP via PKA. PACAP more effective at activating certain pathways. CGRP more abundant in trigeminal system. PACAP more prominent in parasympathetic ganglia.
How They Did This
Review comparing preclinical mouse model data and clinical evidence on PACAP and CGRP in migraine pathophysiology.
Why This Research Matters
For patients who don't respond to CGRP-targeted drugs, PACAP may represent an alternative therapeutic pathway.
The Bigger Picture
Expanding migraine treatment beyond CGRP could help the significant proportion of patients who don't respond adequately to current anti-CGRP therapies.
What This Study Doesn't Tell Us
Review relies heavily on preclinical data — PACAP-targeted therapies are earlier in clinical development than CGRP drugs.
Questions This Raises
- ?Would combining CGRP and PACAP-targeted therapies provide superior migraine relief?
- ?Which patient subgroups would benefit most from PACAP-targeted treatment?
Trust & Context
- Key Stat:
- 2 targets CGRP and PACAP serve complementary roles in migraine with distinct anatomical distributions
- Evidence Grade:
- Review of preclinical and translational evidence — strong scientific rationale but PACAP-targeted drugs are not yet clinically validated.
- Study Age:
- Published in 2025, reflecting the cutting edge of migraine neuroscience.
- Original Title:
- PACAP versus CGRP in migraine: From mouse models to clinical translation.
- Published In:
- Cephalalgia : an international journal of headache, 45(9), 3331024251364242 (2025)
- Authors:
- Pietra, Adriana Della, Kuburas, Adisa(2), Russo, Andrew F(6)
- Database ID:
- RPEP-13053
Evidence Hierarchy
Summarizes existing research without a strict systematic method.
What do these levels mean? →Frequently Asked Questions
What is PACAP and how does it relate to migraine?
PACAP is a neuropeptide involved in migraine, particularly in autonomic symptoms like tearing and nasal congestion. It may be a target for new treatments.
Are there drugs targeting PACAP for migraine?
PACAP-targeted therapies are in early development. Current approved migraine drugs target CGRP, but PACAP could help patients who don't respond to those.
Read More on RethinkPeptides
Cite This Study
https://rethinkpeptides.com/research/RPEP-13053APA
Pietra, Adriana Della; Kuburas, Adisa; Russo, Andrew F. (2025). PACAP versus CGRP in migraine: From mouse models to clinical translation.. Cephalalgia : an international journal of headache, 45(9), 3331024251364242. https://doi.org/10.1177/03331024251364242
MLA
Pietra, Adriana Della, et al. "PACAP versus CGRP in migraine: From mouse models to clinical translation.." Cephalalgia : an international journal of headache, 2025. https://doi.org/10.1177/03331024251364242
RethinkPeptides
RethinkPeptides Research Database. "PACAP versus CGRP in migraine: From mouse models to clinical..." RPEP-13053. Retrieved from https://rethinkpeptides.com/research/pietra-2025-pacap-versus-cgrp-in
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.