Intraepidermal nerves in human skin: PGP 9.5 immunohistochemistry with special reference to the nerve density in skin from different body regions.

The intraepidermal nerves of normal adult human skin were demonstrated by employing a powerful marker of neuronal elements, protein gene product (PGP) 9.5. There were two types of epidermal nerves, free nerve endings and nerves in the Merkel cell-neurite complex. The free nerve endings distributed to, and terminated in, all the strata basale, spinosum and granulosum, and they appeared as thin fibers, mostly varicose, branched or single processed, straight or bent. They existed at every site of the human body, including face, trunk and extremities. However, the densities of these nerves varied in different body parts and areas. The number of nerves decreased from the trunk to the distal parts of the limbs, and small denser 'innervation patches' showed up in the epidermis which were identified in confocal microscopy as one morphologic terminal field coming from the same dermal nerve bundle. This study has confirmed the existence of epidermal nerves in normal adult human skin, and presented a more clear picture than earlier. The difference between densities of epidermal nerves at different body areas implies area-specific functions of the intraepidermal nerve terminals. The observed intraepithelial nerve fibers may have a pain-perceiving role, however, also trophic or immunoregulatory roles can not be excluded.