ArticleNature communications2025
Targeting C1q prevents microglia-mediated synaptic removal in neuropathic pain.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- CD11c + microglia: From basic research to clinical application.Neural regeneration research · 2026Article
- Glial cells in neuropathic pain.Physiological reviews · 2026Review
- Sevoflurane-induced disruption of critical period Arc signaling drives aberrant microglial synaptic pruning and cognitive deficits.Acta pharmacologica Sinica · 2026Article
- IL-33/ST2 Signaling and Microglial Functional-State Transitions After Spinal Cord Injury: Direct Evidence and Mechanistic Hypotheses.International journal of molecular sciences · 2026Review
- Titer- and Intervention Timing-Dependent Functional Effects of AAV9-NeuroD1 Gene Therapy on Spinal Cord Injury.Current issues in molecular biology · 2026Article
- Microglia and neuroinflammation: function, heterogeneity, and crosstalk.Cellular & molecular immunology · 2026Review
- Targeting the PDK1/c-Myc/SOX10 Signaling in Oligodendrocytes Alleviates Neuropathic Pain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lumbar degenerative disease: association of serum complement levels with diagnosis, structural severity, and postoperative prognosis.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Article
- Gnao1 acts as a gatekeeper to alleviate neuropathic pain by silencing pro-nociceptive signaling cascades.The journal of headache and pain · 2026Article
- Astrocytic Redox Homeostasis as a Metabolic Modulator of DNA Damage and Repair in the Ischemic Penumbra.Cells · 2026Review
- Complement-inflammation inhibition via stealth nanomedicine for mild thermo-responsive postoperative on-demand pain management.Materials today. Bio · 2026Article
- Microglia-Mediated Dysfunction of PKCγ Interneurons Underlies the Mechanical Hypersensitivity in Autism.Molecular neurobiology · 2026Article
- Targeting complement and coagulation cascades with Buyang Huanwu Decoction attenuates acute inflammation and enhances neuroprotection in spinal cord injury.Science China. Life sciences · 2026Article
- Role of gut microbiota dysbiosis in podophyllotoxin-induced neurotoxicity in zebrafish: linking purine metabolism to synaptic dysfunction.BMC microbiology · 2026Article
- APOE-mediated lipid transport prevents C1q-related synaptic loss after spinal cord injury via attenuating macrophage lipid stress.Journal of neuroinflammation · 2026Article
- Complement, Inflammasome, and Microglial Crosstalk in Glaucoma: From Neurodegeneration to Immune-Based Precision Therapy.Life (Basel, Switzerland) · 2026Review
- The mechanism of dynamic switching between M1/M2 phenotypes of microglia in neuropathic pain: a narrative review.Frontiers in molecular neuroscience · 2026Review
- Synaptic-immune interactions in neuropathic pain: complement-mediated remodeling of spinal dorsal horn microcircuits.Frontiers in cell and developmental biology · 2026Review
- Engram cell vulnerability in neurodegeneration: from mechanistic insights to therapeutic horizons.Frontiers in aging neuroscience · 2026Review
- PGC-1α Transcriptionally Regulated by ChREBP Mitigates Neuropathic Pain Through Promoting Microglial Fatty Acid Oxidation and Anti-Inflammatory Response.CNS neuroscience & therapeutics · 2026Article
Corrections and comments
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Authors and funding
28 authors.
Funding
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.
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