The skin is innervated by small sensory and autonomic fibers. In the epidermis, sensory fibers are present as unmyelinated C fibers that terminate as free nerve endings. The determination of epidermal nerve fiber (ENF) density using the immunohistochemical method is a powerful tool that provides insight into a population of nerve fibers that is prominently altered in small fiber neuropathy. The superficial location of epidermal nerve fibers allows repeated sampling of these nerves in a relatively noninvasive fashion, and in sites that cannot be assessed through conventional electrodiagnostic techniques. These features have allowed investigators to diagnose diabetic neuropathy earlier in the course of disease. ENF density holds promise as a biomarker for neuropathic pain and is a sensitive indicator of neuropathic progression. Finally, the ability to injure these fibers in a standardized fashion has led to novel measures of human axonal regeneration that may provide a more sensitive ruler by which to assess promising regenerative compounds in clinical trials.
Keywords: Diabetes; PGP 9.5; Schwann cells; epidermal nerve fibers; regeneration; skin biopsy; small fiber neuropathy.