Crosstalk Between Cortical Plasticity and Peripheral Nervous Injury: Insights, Mechanisms, and Future Directions.

INTRODUCTION: Cortical plasticity is essential for functional recovery after peripheral nervous injury (PNI). Different injury types, from compressive to metabolic neuropathies, lead to distinct patterns of cortical reorganization, calling for a better understanding of the mechanisms and treatment options for each injury type. METHODS: This review summarizes current evidence from preclinical, neuroimaging, electrophysiological, and clinical studies on the link between cortical plasticity and PNI. RESULTS: The review describes the key molecular pathways that shape adaptive and maladaptive cortical reorganization across injury types, examines the value of neuroimaging and blood-based biomarkers for tracking plasticity, and evaluates the current evidence for drug and rehabilitation treatments. Major gaps remain, including the limited testing of biomarkers across different injury types, the lack of PNI-specific clinical trials, and the difficulty of applying laboratory findings to personalized treatment. CONCLUSIONS: Moving forward, progress depends on validating biomarkers for each injury type, conducting well-designed trials in PNI patients, and combining drug, rehabilitation, and whole-body treatment approaches. This review offers a practical guide for turning mechanistic knowledge into clinical focus in PNI-related cortical plasticity.