Acta histochem. 99, 301-309 (1997) Gustav Fischer Verlag Aela "isloeMllica Immunohistochemical detection of human skin nerve fibers E. Schulze, M. Witt, T. Fink, A. Hofer and R. H. W. Funk Institute of Anatomy, University Clinic, Technical University Dresden, Fetscher-Strasse 74, D-01307 Dresden, Germany Accepted 8 June 1997 Summary The autonomic nervous system is involved in different functions such as transduction of afferent sensory inputs, trophic actions, modulation of immunologic events and thermoregulation. In the present investigation, we studied the pattern of human autonomic skin innervation with special reference to its relation to blood vessels, hair follicles, sweat glands and sensory receptors. For the first time, two clinically important areas have been compared: the skin of the forearm and of the face. Using indirect immunohistochemistry, we analyzed the distribution of calretinin (CR), calci- tonin gene-related peptide (CGRP), neuropeptide Y (NPY), substance P (SP), neu- rokinin A (NKA), vasoactive intestinal peptide (VIP), nitric oxide synthase (NOS), tyrosine hydroxylase (TH), histamine, serotonin, enkephalin, and, enzyme histo- chemically, NADPH-diaphorase (NADPH-d). In the epidermis, we found nerve fi- bers containing SP, NKA and CGRP. In the dermis, SP-, CR-, VIP-, CGRP- and NKA-positive nerve fibers were detected. Particularly the large nerve fibers con- tained CR. VIP-positive fibers occurred especially around hair follicles and sweat glands. CGRP-positive nerve fibers were located close to the epidermal basal mem- brane, in the wall of blood vessels, and to a lesser extent around hair follicles. Immu- noreactivity for SP and NKA in the dermis was observed predominantly in the papillary layer near the epidermal basal membrane. All neuropeptides tested in this study were also detected in the nerve fibers of the subcutis. Most of them were CGRP- and VIP-positive. They occurred in association with sweat glands and large arteries. NPY-positive nerve fibers are predominant in the wall of arteries, arterioles and veins. Nerve fibers containing NKA and SP were less common and identified only in the walls of large arteries in deeper dermal layers. In double-staining experi- ments, the NADPH-d reaction and reactivity to tubulin revealed a partial co-locali- zation in nerve fibers, blood vessel walls, around glands and ganglionic cells. VIP-positive fibers were more common in the face skin than in the forearm. However, in forearm we detected more NPY-, CGRP-, NKA- and SP-positive nerve fibers than in face skin. These findings are important for future studies on skin disor- ders, such as sensory neuropathies, inflammatory reactions or allergic responses of human skin. Key words: skin - epidermis - dermis - man - neuropeptides - innervation Correspondence to: R H. W. Funk