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Targeting C1q prevents microglia-mediated synaptic removal in neuropathic pain

Author

Listed:
  • Noosha Yousefpour

    (McGill University
    McGill University
    Annexon Biosciences)

  • Shannon N. Tansley

    (McGill University
    McGill University
    McGill University)

  • Samantha Locke

    (McGill University
    McGill University)

  • Behrang Sharif

    (McGill University
    McGill University
    McGill University)

  • Marc Parisien

    (McGill University
    McGill University)

  • Farin B. Bourojeni

    (McGill University
    Montréal)

  • Haley Deamond

    (McGill University
    McGill University)

  • Vidhu Mathur

    (Annexon Biosciences)

  • Nia Rahman-Khan Arana

    (Annexon Biosciences)

  • Jean Sebastien Austin

    (McGill University)

  • Valerie Bourassa

    (McGill University
    McGill University)

  • Chengyang Wang

    (McGill University)

  • Valérie C. Cabana

    (McGill University)

  • Calvin Wong

    (McGill University
    McGill University)

  • Kevin C. Lister

    (McGill University
    McGill University
    McGill University)

  • Rose Rodrigues

    (McGill University
    McGill University
    McGill University)

  • Manon St-Louis

    (McGill University)

  • Marie-Eve Paquet

    (Université Laval
    CERVO Brain Research Centre)

  • Michael C. Carroll

    (Harvard Medical School and Boston Children’s Hospital)

  • Yaisa Andrews-Zwilling

    (Annexon Biosciences)

  • Philippe Seguela

    (McGill University
    McGill University)

  • Artur Kania

    (McGill University
    Montréal
    McGill University
    McGill University)

  • Ted Yednock

    (Annexon Biosciences)

  • Jeffrey S. Mogil

    (McGill University
    McGill University)

  • Yves Koninck

    (McGill University
    CERVO Brain Research Centre
    Université Laval)

  • Luda Diatchenko

    (McGill University
    McGill University
    McGill University)

  • Arkady Khoutorsky

    (McGill University
    McGill University
    McGill University)

  • Alfredo Ribeiro-da-Silva

    (McGill University
    McGill University
    McGill University)

Abstract

Activation of spinal microglia following peripheral nerve injury is a central component of neuropathic pain pathology. While the contributions of microglia-mediated immune and neurotrophic signalling have been well-characterized, the phagocytic and synaptic pruning roles of microglia in neuropathic pain remain less understood. Here, we show that peripheral nerve injury induces microglial engulfment of dorsal horn synapses, leading to a preferential loss of inhibitory synapses and a shift in the balance between inhibitory and excitatory synapse density. This synapse removal is dependent on the microglial complement-mediated synapse pruning pathway, as mice deficient in complement C3 and C4 do not exhibit synapse elimination. Furthermore, pharmacological inhibition of the complement protein C1q prevents dorsal horn inhibitory synapse loss and attenuates neuropathic pain. Therefore, these results demonstrate that the complement pathway promotes persistent pain hypersensitivity via microglia-mediated engulfment of dorsal horn synapses in the spinal cord, revealing C1q as a therapeutic target in neuropathic pain.

Suggested Citation

  • Noosha Yousefpour & Shannon N. Tansley & Samantha Locke & Behrang Sharif & Marc Parisien & Farin B. Bourojeni & Haley Deamond & Vidhu Mathur & Nia Rahman-Khan Arana & Jean Sebastien Austin & Valerie B, 2025. "Targeting C1q prevents microglia-mediated synaptic removal in neuropathic pain," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59849-1
    DOI: 10.1038/s41467-025-59849-1
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    References listed on IDEAS

    as
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