The use of neuropeptide agonists and antagonists will open up new
approaches to the treatment of itch, pain, vasoregulation, and immunological and
Neuropeptides: Their Significance in the Skin
by Joanna Wallengren
The skin protects the body from noxious agents in the environment.
Sensory nerve fibers of the skin transmit sensations of touch, pain and itch.
Neuropeptides such as substance P (SP), neurokinin A (NKA), calcitonin gene-related
peptide (CGRP) and pituitary adenylate cyclase-activating peptide (PACAP) are localized in
epidermal and subepidermal C fibers that transmit these sensations. Opioid peptides
involved in physiological pain control are also found in the peripheral and central
nervous systems. Via antidromic nerve conduction, nerve fibers in the skin participate in
neurogenic inflammation. Blood vessels and sweat glands are innervated by nerve fibers
that contain SP, NKA, CGRP, PACAP and vasoactive intestinal peptide (VIP), which act as
vasodilators. Neuropeptide Y is a potent vasoconstrictor in cardiac and cerebral vascular
beds, but acts as a vasodilator when it occurs in the skin. Some vasoactive peptides such
as endothelin and bradykinin, and other vasoactive molecules such as nitric oxide, seem to
have a cellular rather than neuronal origin in the skin. Some neuropeptides co-exist in
the same nerve fibers and are co-released upon nerve stimulation. They may then cooperate
with each other or antagonize each other. Peptide-degrading enzymes ensure rapid
elimination of mobilized neuropeptides. Many cells of the skin and immunocompetent cells
residing in the skin have been shown to carry receptors for neuropeptides and sometimes to
store or synthesize them. Interaction between the nerve fibers and cells of the immune
system affects allergic skin responses. The immunological effect of a single neuropeptide,
such as CGRP or VIP, may be inhibitory at one concentration but stimulatory at another. SP
and NKA are thought to participate in tissue repair by stimulating the proliferation of
keratinocytes, fibroblasts and endothelial cells. This review summarizes recent findings
regarding the involvement of neuropeptides in the transmission of itch and pain
sensations, and in vasoregulation, immunomodulation and tissue repair.
Neuropeptide-releasing drugs, neuropeptides, and neuropeptide analogues and antagonists
are used as vasoregulatory agents and to alleviate pain or itch. In the future, they may
be used as therapeutic agents to control tissue repair and immune response. © 1999 Prous Science. All rights reserved.
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