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Dorsal root ganglion macrophages contribute to both the initiation and persistence of neuropathic pain

Author

Listed:
  • Xiaobing Yu

    (University of California San Francisco)

  • Hongju Liu

    (University of California San Francisco
    Peking Union Medical College Hospital)

  • Katherine A. Hamel

    (University of California San Francisco)

  • Maelig G. Morvan

    (University of California San Francisco)

  • Stephen Yu

    (University of California San Francisco)

  • Jacqueline Leff

    (University of California San Francisco)

  • Zhonghui Guan

    (University of California San Francisco)

  • Joao M. Braz

    (University of California San Francisco)

  • Allan I. Basbaum

    (University of California San Francisco)

Abstract

Paralleling the activation of dorsal horn microglia after peripheral nerve injury is a significant expansion and proliferation of macrophages around injured sensory neurons in dorsal root ganglia (DRG). Here we demonstrate a critical contribution of DRG macrophages, but not those at the nerve injury site, to both the initiation and maintenance of the mechanical hypersensitivity that characterizes the neuropathic pain phenotype. In contrast to the reported sexual dimorphism in the microglial contribution to neuropathic pain, depletion of DRG macrophages reduces nerve injury-induced mechanical hypersensitivity and expansion of DRG macrophages in both male and female mice. However, fewer macrophages are induced in the female mice and deletion of colony-stimulating factor 1 from sensory neurons, which prevents nerve injury-induced microglial activation and proliferation, only reduces macrophage expansion in male mice. Finally, we demonstrate molecular cross-talk between axotomized sensory neurons and macrophages, revealing potential peripheral DRG targets for neuropathic pain management.

Suggested Citation

  • Xiaobing Yu & Hongju Liu & Katherine A. Hamel & Maelig G. Morvan & Stephen Yu & Jacqueline Leff & Zhonghui Guan & Joao M. Braz & Allan I. Basbaum, 2020. "Dorsal root ganglion macrophages contribute to both the initiation and persistence of neuropathic pain," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13839-2
    DOI: 10.1038/s41467-019-13839-2
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    Cited by:

    1. 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.
    2. Min Jung & Michelle Dourado & James Maksymetz & Amanda Jacobson & Benjamin I. Laufer & Miriam Baca & Oded Foreman & David H. Hackos & Lorena Riol-Blanco & Joshua S. Kaminker, 2023. "Cross-species transcriptomic atlas of dorsal root ganglia reveals species-specific programs for sensory function," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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