Background and aims: Loss of inhibitory synapse and microglia activation play important roles in neuropathic pain. We aimed to investigate whether microglia contribute to the loss of inhibitory synapses in spinal cord.
Methods: Spared nerve injury (SNI) model was established to induce neuropathic pain on rats. Cytochalasin D(60 µM) was intrathecally administrated to inhibit microglial activity. We combined immunofluorescence staining and electron microscopy to examine the physiological roles of microglial activation and the loss of inhibitory synapses in the spinal cord dorsal horn of SNI model. 
Results: Mechanical allodynia was developed on day 3 post-injury and persisted for at least 7 days. Microglia were dramatically increased, whereas marker of Glycinergic synapses was significantly reduced in the lamina II and III of spinal cord dorsal horn. Microglial engulfment assay revealed that more Glycine transporter 2 signals were localized within active microglia (e.g. bigger soma and shorter branches) than inactive microglia, indicating that reactive microglia might stripped pre-synaptic Glycinergic inhibitory synapses via phagocytosis. Intrathecal injection of Cytochalasin D(60 µM) significantly decreased microglial activity and relieved mechanical allodynia. Notably, the loss of Glycinergic synapse was completely reversed upon microglia inhibition. 
Conclusion: Microglia might enhance neuropathic pain by engulfing Glycinergic synapses in spinal cord.

MICROGLIA PROMOTE NEUROPATHIC PAIN VIA ELIMINATING GABAERGIC SYNAPSES IN SPINAL CORD