The autonomic nervous system is involved in different functions such a
s transduction of afferent sensory inputs, trophic actions, modulation
of immunologic events and thermoregulation. In the present investigat
ion, we studied the pattern of human autonomic skin innervation with s
pecial reference to its relation to blood vessels, hair follicles, swe
at glands and sensory receptors. For the first time, two clinically im
portant areas have been compared: the skin of the forearm and of the f
ace. Using indirect immunohistochemistry, we analyzed the distribution
of calretinin (CR), calcitonin gene-related peptide (CGRP), neuropept
ide Y (NPY), substance P (SP), neurokinin A (NKA), vasoactive intestin
al peptide (VIP), nitric oxide synthase (NOS), tyrosine hydroxylase (T
H), histamine, serotonin, enkephalin, and, enzyme histochemically, NAD
PH-diaphorase (NADPH-d). In the epidermis, we found nerve fibers conta
ining SP, NKA and CGRP. In the dermis, SP-, CR-, VIP-, CGRP-and NKA-po
sitive nerve fibers were detected. Particularly the large nerve fibers
contained CR. VIP-positive fibers occurred especially around hair fol
licles and sweat glands. CGRP-positive nerve fibers were located close
to the epidermal basal membrane, in the wall of blood vessels, and to
a lesser extent around hair follicles. Immunoreactivity for SP and NK
A 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 w
ere CGRP-and VIP-positive. They occurred in association with sweat gla
nds and large arteries. NPY-positive nerve fibers are predominant in t
he wall of arteries, arterioles and veins. Nerve fibers containing NKA
and SP were less common and identified only in the walls of large art
eries in deeper dermal layers. In double-staining experiments, the NAD
PH-d reaction and reactivity to tubulin revealed a partial co-localiza
tion 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 import
ant for future studies on skin disorders, such as sensory neuropathies
, inflammatory reactions or allergic responses of human skin.