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TRPM8 contributes to sex dimorphism by promoting recovery of normal sensitivity in a mouse model of chronic migraine

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Listed:
  • David Alarcón-Alarcón

    (Universidad Miguel Hernández de Elche)

  • David Cabañero

    (Universidad Miguel Hernández de Elche)

  • Jorge Andrés-López

    (Universidad Miguel Hernández de Elche)

  • Magdalena Nikolaeva-Koleva

    (Universidad Miguel Hernández de Elche)

  • Simona Giorgi

    (Universidad Miguel Hernández de Elche)

  • Gregorio Fernández-Ballester

    (Universidad Miguel Hernández de Elche)

  • Asia Fernández-Carvajal

    (Universidad Miguel Hernández de Elche)

  • Antonio Ferrer-Montiel

    (Universidad Miguel Hernández de Elche)

Abstract

TRPA1 and TRPM8 are transient receptor potential channels expressed in trigeminal neurons that are related to pathophysiology in migraine models. Here we use a mouse model of nitroglycerine-induced chronic migraine that displays a sexually dimorphic phenotype, characterized by mechanical hypersensitivity that develops in males and females, and is persistent up to day 20 in female mice, but disappears by day 18 in male mice. TRPA1 is required for development of hypersensitivity in males and females, whereas TRPM8 contributes to the faster recovery from hypersensitivity in males. TRPM8-mediated antinociception effects required the presence of endogenous testosterone in males. Administration of exogenous testosterone to females and orchidectomized males led to recovery from hypersensitivity. Calcium imaging and electrophysiological recordings in in vitro systems confirmed testosterone activity on murine and human TRPM8, independent of androgen receptor expression. Our findings suggest a protective function of TRPM8 in shortening the time frame of hypersensitivity in a mouse model of migraine.

Suggested Citation

  • David Alarcón-Alarcón & David Cabañero & Jorge Andrés-López & Magdalena Nikolaeva-Koleva & Simona Giorgi & Gregorio Fernández-Ballester & Asia Fernández-Carvajal & Antonio Ferrer-Montiel, 2022. "TRPM8 contributes to sex dimorphism by promoting recovery of normal sensitivity in a mouse model of chronic migraine," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33835-3
    DOI: 10.1038/s41467-022-33835-3
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    References listed on IDEAS

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    1. Diana M. Bautista & Jan Siemens & Joshua M. Glazer & Pamela R. Tsuruda & Allan I. Basbaum & Cheryl L. Stucky & Sven-Eric Jordt & David Julius, 2007. "The menthol receptor TRPM8 is the principal detector of environmental cold," Nature, Nature, vol. 448(7150), pages 204-208, July.
    2. Ruozhu Zhao & Xin Chen & Weiwei Ma & Jinyu Zhang & Jie Guo & Xiu Zhong & Jiacheng Yao & Jiahui Sun & Julian Rubinfien & Xuyu Zhou & Jianbin Wang & Hai Qi, 2020. "A GPR174–CCL21 module imparts sexual dimorphism to humoral immunity," Nature, Nature, vol. 577(7790), pages 416-420, January.
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