• J Headache Pain · Jan 2025

    Review

    Revisiting substance P in migraine: a methodological approach inspired by anti-CGRP and anti-PACAP success.

    • Lanfranco Pellesi and Lars Edvinsson.
    • Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, 5230, Denmark. lpellesi@health.sdu.dk.
    • J Headache Pain. 2025 Jan 31; 26 (1): 2222.

    AbstractSubstance P, previously dismissed as a therapeutic target for migraine due to the failure of neurokinin-1 receptor antagonists, warrants renewed attention. Building on the success of therapies targeting the calcitonin gene-related peptide (CGRP) system and pituitary adenylate cyclase-activating peptide (PACAP) in migraine prevention, which highlight the importance of targeting peptides, this proposal reexamines substance P as a mediator in migraine pathophysiology. Using an established methodological framework, migraine-inducing properties of substance P can be evaluated through randomized, double-blind, placebo-controlled crossover studies involving healthy volunteers and individuals with a history of migraine. This approach aims to establish proof of concept for substance P's role in migraine, laying the groundwork for investigations with animal and cell-based models and advancing the development of innovative treatments for patients refractory to current therapies.© 2025. The Author(s).

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