Systemic PACAP-38 disrupts motion-induced thermoregulation and balance in mice, with some sex-specific effects, paralleling known CGRP effects on vestibular function.
Sex-specificPACAP-38 increased postural sway in female mice only, reflecting known migraine sex differences
What the researchers found
IP PACAP-38 significantly disrupted motion-induced thermoregulation (nausea proxy) in both sexes, increased postural sway in females, and caused balance deficits — comparable to known CGRP effects.
Why it matters
Understanding how PACAP affects vestibular function supports developing anti-PACAP therapies for migraine patients who experience significant nausea, dizziness, and balance problems.
The numbers in context
IP injection of PACAP-38 and CGRP in C57BL/6J mice; PACAP blunted tail vasodilation, increased postural sway (females), impaired balance beam; CGRP affected rotarod.
How the study worked
Preclinical study in C57BL/6J mice using IP injection of PACAP-38 and CGRP with motion-induced thermoregulation, center of pressure, rotarod, and balance beam behavioral assays.
Who was studied
C57BL/6J wildtype mice
What this study cannot tell us
Mouse model — vestibular and nausea responses may differ in humans; IP delivery may not reflect natural PACAP release patterns during migraine; behavioral proxies for nausea have inherent limitations.
How to read the evidence
Preclinical mouse study with well-characterized behavioral assays; translational relevance to human migraine supported by existing PACAP/CGRP biology.
When this study was published
Published in 2025, advancing the understanding of PACAP's role in migraine-associated vestibular dysfunction.
The bigger picture
As anti-CGRP therapies become established for migraine, PACAP represents the next frontier — this study provides preclinical evidence that PACAP-targeted treatments could address vestibular migraine symptoms that anti-CGRP drugs may not fully resolve.
Questions still open
- Would anti-PACAP antibodies reduce vestibular migraine symptoms in human patients?
- Why does PACAP-38 affect postural sway differently in male vs female mice?
Common questions
What is PACAP and how is it related to migraine?
Why do migraines cause nausea and dizziness?
Read the original research
Comparing the impact of systemic pituitary adenylate-cyclase-activating polypeptide (PACAP) and calcitonin gene-related peptide (CGRP) on motion-induced nausea and balance behaviors in mice.
PloS one, 20(11), e0334444
Citation
Rahman, Shafaqat M; Dweh, Abigail; Luebke, Anne E. (2025). Comparing the impact of systemic pituitary adenylate-cyclase-activating polypeptide (PACAP) and calcitonin gene-related peptide (CGRP) on motion-induced nausea and balance behaviors in mice.. PloS one, 20(11), e0334444. https://doi.org/10.1371/journal.pone.0334444