We combined multimodal (rsfMRI,M MRS, VBM) neuroimaging to longitudinally monitor changes in brain metabolism, structure and connectivity using the spared nerve injury (SNI) mouse model of chronic neuropathic pain. Voxel-based morphometry demonstrated volume decrease in all brain sites assessed. Global and local network changes after SNI disappeared over time, except the nucleus accumbens, prefrontal cortex and hippocampus. Connectivity changes were accompanied by enhanced glutamate levels in the hippocampus. We suggest that hippocampal hyperexcitability may alter synaptic plasticity within the nucleus accumbens, circadian motor activity and emotionality during pain chronification.