Microglial CR3-mediated synaptic pruning in the dmPFC promotes the generation and maintenance of chronic muscle pain via glutamatergic dysfunction - PubMed
5 hours ago
- #microglia-neuron interaction
- #glutamatergic dysfunction
- #chronic muscle pain
- Chronic muscle pain (CMP) is prevalent, often comorbid with emotional disorders, and has a high recurrence risk.
- Suppressed glutamatergic neuronal excitability and reduced synaptic plasticity in the dorsomedial prefrontal cortex (dmPFC) were observed in CMP rats.
- Activation of dmPFC glutamatergic neurons alleviated pain and anxiety-like behaviors.
- Single-cell RNA sequencing showed upregulated proinflammatory microglia and complement receptor 3 (CR3) in the dmPFC, linked to reduced neuronal excitability.
- Hyperactive glutamatergic neurons induced microglial activation, proliferation, polarization, and chemotaxis.
- Inhibition of microglia or knockdown of microglial CR3 restored neuronal excitability and synaptic plasticity, reducing hyperalgesia and anxiety-like behaviors.
- Microglial CR3-dependent synaptic pruning underlies glutamatergic dysfunction, playing a key role in CMP generation and maintenance.
- Findings suggest novel microglia-neuron interactions and potential therapeutic targets for CMP and related emotional disorders.