Role of skin biopsy in the diagnosis of peripheral neuropathic pain

Evaluation of epidermal nerve fiber density (ENFD) allows objective, pathologic, and minimally invasive assessment of small myelinated and unmyelinated cutaneous axons. In addition to providing diagnostic confirmation of neuropathies affecting these “small fibers,” this procedure has advanced clinical care by dramatically increasing awareness of the role of small myelinated and unmyelinated axons in disorders of peripheral nerve and in neuropathic pain. This review highlights the technical aspects of skin biopsy for ENFD determination, the role of skin biopsy in the diagnosis of small-fiber neuropathy and ganglionopathy, and the diagnostic approach to the patient with peripheral neuropathic pain.