Pathology of nerve terminal degeneration in the skin

To characterize the pathology of epidermal nerve degeneration and regenerat ion, we investigated temporal and spatial changes in skin innervation of th e mouse footpad. Within 24 hours after sciatic nerve axotomy, terminals of epidermal nerves appeared swollen and there was a mild reduction in epiderm al nerve density (5.7 +/- 2.8 vs 12.7 +/- 2.2 fibers/mm, p < 0.04). Epiderm al nerves completely disappeared by 48 hours (0.2 +/- 0.2 vs 14.2 +/- 0.9 f ibers/mm, p < 0.001). Concomitant with the disappearance of epidermal nerve s, the immunocytochemical pattern of the subepidermal nerve plexus became f ragmented. At the electron microscopic level, the axoplasm of degenerating dermal nerves was distended with organelles and later became amorphous. Beg inning from day 28 after axotomy, collateral sprouts from the adjacent saph enous nerve territory extended into the denervated area with a beaded appea rance. They never penetrated the epidermal-dermal junction to innervate the epidermis. In contrast, 3 months after nerve crushing, the epidermis on th e surgery side resumed a normal innervation pattern as the epidermis on the control side (10.3 +/- 3.9 vs 10.6 +/- 1.5 fibers/mm, p = 0.1). This study demonstrates the characteristics of degenerating and regenerating nerves, and suggests that successful reinnervation mainly originates from regenerat ing nerves of the original nerve trunks. All these findings provide qualita tive and quantitative information for interpreting the pathology of cutaneo us nerves.