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The Journal of Neuroscience, November 1, 1998, 18(21):8947-8959
Intradermal Injection of Capsaicin in Humans Produces
Degeneration and Subsequent Reinnervation of Epidermal Nerve Fibers:
Correlation with Sensory Function
Donald A.
Simone1, 2,
Maria
Nolano3,
Timothy
Johnson4,
Gwen
Wendelschafer-Crabb4, and
William R.
Kennedy4
Departments of 1 Psychiatry, 2 Preventive
Sciences, and 4 Neurology, University of Minnesota,
Minneapolis, Minnesota 55455, and 3 Salvatore Maugeri
Foundation, Campoli M.T. (BN), Italy
The ability of capsaicin to excite and subsequently to desensitize
a select group of small sensory neurons has made it a useful tool to
study their function. For this reason, application of capsaicin to the
skin has been used for a variety of painful syndromes. We examined
whether intradermal injection of capsaicin produced morphological
changes in cutaneous nerve fibers that would account for its analgesic
properties by comparing cutaneous innervation in capsaicin-treated skin
with psychophysical measures of sensation. At various times after
capsaicin injection, nerve fibers were visualized immunohistochemically
in skin biopsies and were quantified. In normal skin the epidermis is
heavily innervated by nerve fibers immunoreactive for protein gene
product (PGP) 9.5, whereas fibers immunoreactive for substance P (SP)
and calcitonin gene-related peptide (CGRP) are typically associated
with blood vessels. There was nearly complete degeneration of epidermal
nerve fibers and the subepidermal neural plexus in capsaicin-treated
skin, as indicated by the loss of immunoreactivity for PGP 9.5 and
CGRP. The effect of capsaicin on dermal nerve fibers immunoreactive for
SP was less obvious. Capsaicin decreased sensitivity to pain produced by sharp mechanical stimuli and nearly eliminated heat-evoked pain
within the injected area. Limited reinnervation of the epidermis and
partial return of sensation occurred 3 weeks after treatment; reinnervation of the epidermis was ~25% of normal, and sensation improved to 50-75% of normal. These data show that sensory
dysfunction after capsaicin application to the skin results from rapid
degeneration of intracutaneous nerve fibers.
Key words:
pain; analgesia; protein gene product 9.5; intracutaneous
nerves; immunohistochemistry; confocal microscopy
Copyright © 1998 Society for Neuroscience 0270-6474/98/18218947-13$05.00/0
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