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NAAA-regulated lipid signaling in monocytes controls the induction of hyperalgesic priming in mice

Author

Listed:
  • Yannick Fotio

    (University of California Irvine)

  • Alex Mabou Tagne

    (University of California Irvine)

  • Erica Squire

    (University of California Irvine)

  • Hye-lim Lee

    (University of California Irvine)

  • Connor M. Phillips

    (University of California Irvine)

  • Kayla Chang

    (University of California Irvine)

  • Faizy Ahmed

    (University of California Irvine)

  • Andrew S. Greenberg

    (Tufts University)

  • S. Armando Villalta

    (University of California Irvine
    University of California Irvine)

  • Vanessa M. Scarfone

    (University of California Irvine)

  • Gilberto Spadoni

    (Università di Urbino “Carlo Bo,”)

  • Marco Mor

    (Università di Parma)

  • Daniele Piomelli

    (University of California Irvine
    University of California Irvine
    University of California Irvine)

Abstract

Circulating monocytes participate in pain chronification but the molecular events that cause their deployment are unclear. Using a mouse model of hyperalgesic priming (HP), we show that monocytes enable progression to pain chronicity through a mechanism that requires transient activation of the hydrolase, N-acylethanolamine acid amidase (NAAA), and the consequent suppression of NAAA-regulated lipid signaling at peroxisome proliferator-activated receptor-α (PPAR-α). Inhibiting NAAA in the 72 hours following administration of a priming stimulus prevented HP. This effect was phenocopied by NAAA deletion and depended on PPAR-α recruitment. Mice lacking NAAA in CD11b+ cells – monocytes, macrophages, and neutrophils – were resistant to HP induction. Conversely, mice overexpressing NAAA or lacking PPAR-α in the same cells were constitutively primed. Depletion of monocytes, but not resident macrophages, generated mice that were refractory to HP. The results identify NAAA-regulated signaling in monocytes as a control node in the induction of HP and, potentially, the transition to pain chronicity.

Suggested Citation

  • Yannick Fotio & Alex Mabou Tagne & Erica Squire & Hye-lim Lee & Connor M. Phillips & Kayla Chang & Faizy Ahmed & Andrew S. Greenberg & S. Armando Villalta & Vanessa M. Scarfone & Gilberto Spadoni & Ma, 2024. "NAAA-regulated lipid signaling in monocytes controls the induction of hyperalgesic priming in mice," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46139-5
    DOI: 10.1038/s41467-024-46139-5
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