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Haanes and Hkan Ashina 2025 expanded migraine therapeutics beyond CGRP, spotlighting several new biological pathways with translational promise PACAP emerged as the most advanced new target, confirmed as a CGRP-independent pathway with early preventive efficacy Substance P returned as a validated human headache trigger, reopening discussion around neurokinin-based treatments Vascular KATP channels appear to act as a convergence point for multiple migraine mediators, positioning them as a potential broad-spectrum target TRPM3 channels link trigeminal activation with sex hormone modulation, offering insight into sex differences in migraine biology PAR2 highlights neuroimmune crosstalk as a novel therapeutic direction, with preclinical antibody data showing migraine-like pain reduction Bottom line: migraine treatment is moving toward mechanism-based precision care, with multiple new targets now opening doors beyond CGRP More Cephalalgia 2025 editorials coming soon stay tuned

Montagnese, S., Amodio, P

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[DOI] [PubMed] [Google Scholar] Calvani M., Carta A., Benedetti N., Iannuccelli M., Caruso G