Autonomic modulation of neuroplasticity in spinal cord injury rehabilitation: insights from a narrative review

Spinal Cord Injury (SCI) causes persistent autonomic dysregulation, which is not merely a clinical epiphenomenon, but a mechanistic condition shaping the neurochemical, neurovascular, and immuno-endocrine milieu in which plasticity unfolds. Yet, the modulatory role of the Autonomic Nervous System (ANS) in post-injury circuit reorganization remains insufficiently integrated in rehabilitation paradigms. This narrative review synthesizes emerging evidence (2020-2025) describing how sympatho-vagal dynamics constrain or enable adaptive plasticity following SCI, and surveys therapeutic strategies that intentionally leverage autonomic modulation to amplify recovery. Mechanistically, autonomic tone influences neuronal excitability, perfusion, neurotrophin signaling (notably Brain-Derived Neurotrophic Factor (BDNF)/Tropomyosin receptor kinase B (TrkB)), and microglia-dependent inflammatory states. Recurrent sympathetic surges during Autonomic Dysreflexia (AD) bias networks toward maladaptive phenotypes, whereas enhanced vagal flexibility promotes neurotrophin availability, homeostatic excitability, and synaptic strengthening. Interventions including Vagus Nerve Stimulation (VNS), paired with task-specific training, respiratory-based protocols, Heart Rate Variability (HRV) biofeedback, and individualized aerobic exercise demonstrate promising autonomic and functional effects. Altogether, these observations support the view that autonomic modulation is a mechanistic boundary condition for post-injury plasticity, rather than a secondary consequence of SCI. Future work requires rigorously powered, multimodal trials integrating autonomic biomarkers-especially HRV-with neurophysiological endpoints to refine dose-specific protocols and accelerate translation into precision-based rehabilitation.