Cold receptor TRPM8 as a target for migraine-associated pain and affective comorbidities.

Journal: The journal of headache and pain
Published Date: Jun 23, 2025

Abstract

BACKGROUND: Genetic variations in the Trpm8 gene that encodes the cold receptor TRPM8 have been linked to protection against polygenic migraine, a disabling condition primarily affecting women. Noteworthy, TRPM8 has been recently found in brain areas related to emotional processing, suggesting an unrecognized role in migraine comorbidities. Here, we use mouse behavioural models to investigate the role of Trpm8 in migraine-related phenotypes. Subsequently, we test the efficacy of rapamycin, a clinically relevant TRPM8 agonist, in these behavioural traits and in human induced pluripotent stem cell (iPSC)-derived sensory neurons.

Authors

  • David Cabañero
    Institute of Research, Development and Innovation in Healthcare Biotechnology of Elche (IDiBE), University Miguel Hernández of Elche, Altabix-3, 5, Elche, 03207, Spain. dcabanero@umh.es.
  • Edward P Carter
    Department of Life Sciences, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
  • Rafael González-Cano
    Department of Pharmacology, Faculty of Medicine and Biomedical Research Center (Neurosciences Institute), Biosanitary Research Institute ibs.GRANADA, University of Granada, Granada, 18016, Spain.
  • Enrique J Cobos
    Department of Pharmacology, Faculty of Medicine and Biomedical Research Center (Neurosciences Institute), Biosanitary Research Institute ibs.GRANADA, University of Granada, Granada, 18016, Spain.
  • Asia Fernández-Carvajal
    Institute of Research, Development and Innovation in Healthcare Biotechnology of Elche (IDiBE), University Miguel Hernández of Elche, Altabix-3, 5, Elche, 03207, Spain. asia.fernandez@umh.es.
  • Antonio Ferrer-Montiel
    Institute of Research, Development and Innovation in Healthcare Biotechnology of Elche (IDiBE), University Miguel Hernández of Elche, Altabix-3, 5, Elche, 03207, Spain. aferrer@umh.es.

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