Large-scale functional brain network organization is largely preserved in neuropathic pain despite selective circuit-level adaptations

Neuropathic pain results from damage to the nervous system and causes persistent changes in brain function that contribute to chronic pain. Understanding how these changes evolve over time is essential for identifying the mechanisms that sustain the disease. Here we show how brain-wide communication changes during the development and persistence of neuropathic pain in male mice using resting-state functional ultrasound imaging in awake and anesthetized animals. Pain onset is associated with transient increases in communication between brain regions involved in sensory, motivational, and emotional processing, whereas the persistent phase shows reduced communication within movement-related networks. Animals that undergo surgery without nerve injury also display lasting changes, revealing brain plasticity independent of neuropathic pain. Despite these network alterations, the overall organization of spontaneous brain activity remains stable. These findings reveal phase-dependent adaptations in brain circuits while preserving global resting-state brain dynamics. We used functional ultrasound imaging to characterize longitudinal changes in static and dynamic resting-state functional connectivity in awake and anesthetized mice during neuropathic pain. Neuropathic pain induces selective, stage-dependent circuit adaptations while largely preserving the global organization and temporal dynamics of large-scale brain networks.