Degeneration of nociceptive nerve terminals in human peripheral neuropathy

Patients with peripheral neuropathy have symptoms involving small-diameter nociceptive nerves and elevated thermal thresholds. Nociceptive nerves term inate in the epidermis of the skin and are readily demonstrated with the ne uronal marker, protein gene product 9.5 (PGP 9.5). To investigate the patho logical characteristics of elevated thermal thresholds, we performed PGP 9. 5 immunocytochemistry on 3 mm punch skin biopsies (the forearm and the leg) from 55 normal subjects and 35 neuropathic patients. Skin innervation was evaluated by quantifying epidermal nerve densities. Epidermal nerve densiti es were reduced in neuropathic patients compared to normal subjects. Epider mal nerve densities were variably correlated with thermal thresholds. The p roportion of neuropathic patients with reduced epidermal nerve densities wa s larger than the proportion of neuropathic patients with elevated thermal thresholds. These results indicated that degeneration of epidermal nerve te rminals preceded the elevation of thermal thresholds. Skin biopsy together with immunocytochemical demonstration of epidermal innervation offers a new approach to evaluate small-fiber sensory neuropathy. NeuroReport 12:787-79 2 (C) 2001 Lippincott Williams & Wilkins.