Effects of peripheral nerve damage on promoting maladaptive plasticity in the spinal cord and brain

Peripheral nerves can acquire damage through trauma, demyelinating diseases, inflammatory or immune-mediated insults, cancer, metabolic disorders, medications, toxins, and others. Damage may occur to motor, sensory, or pain fibres, or a combination, resulting in dysfunction to movement execution, sensory perception, and pain processing. Electrodiagnostic studies of the peripheral nerves, muscles, and spinal reflexes can be used to diagnose peripheral nerve damage, detect resultant changes in the central nervous system, and track the progress of neural repair or deterioration. Through interactions, or loss of interactions, damage to peripheral nerves results in lasting maladaptive changes in the central nervous system. These changes can result in neuropathic pain, impaired sensorimotor function, brain and spinal atrophy, and functional reorganization of neural networks. This review provides an overview of anatomy and physiology of the peripheral and central nervous system. A thorough summary of the etiologies that can result in acquired peripheral nerve damage is presented. For each etiology, the mechanisms behind damage to the affected peripheral nerves, their functional consequences, and electrodiagnostic characteristics are described. A description of how peripheral nerve damage results in maladaptive changes throughout the nervous system is given, supported by examples from many etiologies. The boundary of knowledge of various types of peripheral nerve damage, including their mechanisms-of-action, electrodiagnostic characteristics, and maladaptive changes is summarized. The review ends with a discussion of neuromodulation therapies applied throughout the nervous system that have the potential to reduce or reverse maladaptive changes resulting from peripheral nerve damage, and priority areas for future research.