Microglia are known to be involved in the structural changes of synapses and axons. Microglia in the spinal cord are critical for the development of neuropathic pain. However, it remains unclear whether microglia involve structural changes of neurons during neuropathic pain. Here, we investigated the above possibilities using an orofacial neuropathic pain model. After infraorbital nerve injury, the density of DbH immunofluorescence in the trigeminal spinal subnucleus caudalis (Vc) was decreased, while DbH positive particles increased within microglia. DbH-positive particles in microglia were positive for MHC-I. Surprisingly, MHC-I immunofluorescence was also observed in microglial processes. To clarify whether MHC-I secretion from microglia induces the uptake of DbH-positive axons, exosomes were isolated from primary cultured microglia. Intracisternal administration of exosomes from IFNgannma-stimulated microglia elicited mechanical allodynia in the whisker pad and downregulation of DbH expression in the Vc. In contrast, exosomes from IFNgannma-stimulated MHC-I knockdown microglia unchanged pain sensitivity and DbH expression in the Vc. These results suggest that activated microglia-derived MHC-I causes the reduction of NAergic axons, culminating in enhanced neuronal activity in the Vc.