Evaluation and treatment of painful peripheral polyneuropathy

Pain is a common component of sensory peripheral polyneuropathy and occurs primarily as a consequence of injury to small, unmyelinated C-fiber nerve axons. This class of fibers is particularly vulnerable to metabolic injury, and the neuropathy manifests in a length-dependent pattern. Diabetes mellitus, prediabetes associated with insulin resistance, toxins, and drugs are common causes of painful neuropathy, but a substantial percentage are idiopathic. Pathogenesis of neuropathic pain involves loss of peripheral axons and inappropriate peripheral and central adaptation of neuronal signaling to this loss. Treatment of painful neuropathy should be directed at removing the offending metabolic injury, if possible. Antiepileptic drugs, tricyclic antidepressants, opiates, and other treatments have shown efficacy in clinical trials for symptomatic relief of neuropathic pain.