ArticlePloS one2025
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.
Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Pituitary adenylate-cyclase-activating polypeptide (PACAP), particularly its dominant isoform PACAP-38, is implicated in migraine and represents a promising therapeutic target. We investigated if intraperitoneally delivered (IP) PACAP-38 impacts motion-induced nausea, postural sway, and imbalance in C57BL/6J wildtype mice using the motion-induced thermoregulation, center of pressure (CoP), rotarod, and balance beam assays. We also assessed systemic Calcitonin Gene-Related Peptide's (CGRP) effects on these behaviors in parallel. Our findings indicate that IP PACAP-38 significantly disrupts motion-induced thermoregulation in mice, with notable blunting of tail vasodilation responses in both sexes. Additionally, PACAP-38 administration increased postural sway in female mice only and caused balance beam imbalances. Contrary to IP CGRP, IP PACAP-38 did not affect rotarod performance when mice were trained on a dowel with 1.5 cm radius. Our findings provide preclinical evidence supporting a potential role of PACAP-38 in vestibular migraine pathophysiology. Future research will explore if PACAP antagonism can protect against PACAP-38's effects on nausea and balance behaviors, relevant to treatment of vestibular migraine (VM), especially for patients unresponsive to triptans or CGRP-targeting therapies.
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