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Schwann cell C5aR1 co-opts inflammasome NLRP1 to sustain pain in a mouse model of endometriosis

Author

Listed:
  • Mustafa Titiz

    (University of Florence)

  • Lorenzo Landini

    (University of Florence)

  • Daniel Souza Monteiro de Araujo

    (University of Florence)

  • Matilde Marini

    (University of Florence)

  • Viola Seravalli

    (University of Florence)

  • Martina Chieca

    (University of Florence)

  • Pasquale Pensieri

    (University of Florence)

  • Marco Montini

    (University of Florence)

  • Gaetano De Siena

    (University of Florence)

  • Benedetta Pasquini

    (University of Florence)

  • Silvia Vannuccini

    (University of Florence)

  • Luigi Francesco Iannone

    (University of Florence)

  • Thiago M. Cunha

    (University of São Paulo)

  • Giulia Brancolini

    (FloNext srl)

  • Elisa Bellantoni

    (University of Florence)

  • Irene Scuffi

    (University of Florence)

  • Alessandra Mastricci

    (University of Florence)

  • Martina Tesi

    (University of Florence)

  • Mariarosaria Di Tommaso

    (University of Florence)

  • Felice Petraglia

    (University of Florence)

  • Pierangelo Geppetti

    (University of Florence
    New York University
    New York University)

  • Romina Nassini

    (University of Florence)

  • Francesco De Logu

    (University of Florence)

Abstract

Over 60% of women with endometriosis experience abdominopelvic pain and broader pain manifestations, including chronic back pain, fibromyalgia, chronic fatigue, vulvodynia, and migraine. Although the imbalance of proinflammatory mediators, including the complement component C5a, is associated with endometriosis-related pain, the mechanisms causing widespread pain and the C5a role remain unclear. Female mice and women with endometriosis exhibit increased plasma C5a levels and pain. We hypothesize the Schwann cells involvement in endometriotic pain. Here, we show that silencing the C5a receptor (C5aR1) in Schwann cells blocks the C5a-induced activation of the NLRP1 inflammasome and subsequent release of interleukin-1β (IL-1β). Macrophages, recruited to sciatic/trigeminal nerves by IL-1β from Schwann cells, increase oxidative stress, which activates the proalgesic TRPA1 pathway, resulting in widespread pain. These findings reveal a pathway involving Schwann cell C5aR1, NLRP1/IL-1β activation, macrophage recruitment, oxidative stress, and TRPA1 engagement, contributing to pain in a mouse model of endometriosis.

Suggested Citation

  • Mustafa Titiz & Lorenzo Landini & Daniel Souza Monteiro de Araujo & Matilde Marini & Viola Seravalli & Martina Chieca & Pasquale Pensieri & Marco Montini & Gaetano De Siena & Benedetta Pasquini & Silv, 2024. "Schwann cell C5aR1 co-opts inflammasome NLRP1 to sustain pain in a mouse model of endometriosis," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54486-6
    DOI: 10.1038/s41467-024-54486-6
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    References listed on IDEAS

    as
    1. Francesco De Logu & Romina Nassini & Alan Hegron & Lorenzo Landini & Dane D. Jensen & Rocco Latorre & Julia Ding & Matilde Marini & Daniel Souza Monteiro de Araujo & Paulina Ramírez-Garcia & Michael W, 2022. "Schwann cell endosome CGRP signals elicit periorbital mechanical allodynia in mice," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Francesco De Logu & Romina Nassini & Serena Materazzi & Muryel Carvalho Gonçalves & Daniele Nosi & Duccio Rossi Degl’Innocenti & Ilaria M. Marone & Juliano Ferreira & Simone Li Puma & Silvia Benemei &, 2017. "Schwann cell TRPA1 mediates neuroinflammation that sustains macrophage-dependent neuropathic pain in mice," Nature Communications, Nature, vol. 8(1), pages 1-16, December.
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