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Drug News Perspect 1999, 12(7): 401
ISSN 0214-0934
e-ISSN
Copyright 1999 Clarivate
CCC: 0214-0934
 

LOOKING AHEAD

The use of neuropeptide agonists and antagonists will open up new approaches to the treatment of itch, pain, vasoregulation, and immunological and irritative reactions.

Neuropeptides: Their Significance in the Skin

by Joanna Wallengren


Summary

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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