DISTINCT REHABILITATION STRATEGIES DRIVE DIFFERENTIAL SENSORIMOTOR RECOVERY AND BRAIN ACTIVATION AFTER SPINAL CORD INJURY IN MICE

Spinal cord injury (SCI) leads to severe sensorimotor impairments, often accompanied by neuropathic pain. Evidence suggests that activity-based rehabilitation, the only intervention shown to independently promote motor recovery, engages a widespread network of spinal and supraspinal structures. However, different rehabilitative approaches may result in distinct outcomes. Pain management remains challenging, as current treatments are often insufficient or have significant side effects. This study aimed to compare two rehabilitative strategies and evaluate their impact on motor function and pain perception. C57Bl6/J mice underwent an incomplete C5 spinal cord transection, followed by eight weeks of either task-specific directed rehabilitation, free unspecific rehabilitation in an enriched environment, or no rehabilitation. Motor performance and pain perception were assessed at 1, 3, 5, and 9 weeks post-injury. At the end of the study, spinal cord sections were stained with cresyl violet and luxol blue to characterize lesion extent and identify affected spinal tracts. FosB expression was assessed by immunofluorescence in several cortical and subcortical regions. Both rehabilitative strategies, particularly task-specific training, improved gross forelimb motor function. Pain outcomes also improved in rehabilitated mice compared to non-rehabilitated ones. We observed a FosB expression pattern that varied among rehabilitation models in a region-specific manner, indicating that particular regions are recruited under different rehabilitation modalities. These findings reinforce the benefits of activity-based interventions in SCI recovery and highlight that different rehabilitation strategies may differentially impact motor and sensory outcomes. Additionally, the region-specific activation pattern may help to direct neuromodulatory strategies towards particular regions.