Targeting C1q prevents microglia-mediated synaptic removal in neuropathic pain.

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

SUBMITTER: Yousefpour N 

PROVIDER: S-EPMC12085617 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature