Nerve growth factor/p38 signaling increases intraepidermal nerve fiber densities
in painful neuropathy of type 2 diabetes.
Authors Cheng HT, Dauch JR, Hayes JM, Yanik BM, Feldman EL
Submitted By Eva Feldman on 2/22/2012
Status Published
Journal Neurobiology of disease
Year 2012
Date Published 1/1/2012
Volume : Pages 45 : 280 - 287
PubMed Reference 21872660
Abstract Painful diabetic neuropathy (PDN) is a common, yet devastating complication of
type 2 diabetes. At this time, there is no objective test for diagnosing PDN. In
the current study, we measured the peptidergic intraepidermal nerve fiber
densities (IENFD) from hind paws of the db/db mouse, an animal model for type 2
diabetes, during the period of mechanical allodynia from 6 to 12 weeks of age.
Intraepidermal nerve fibers (IENF) of the hind footpads were identified by
protein gene product (PGP) 9.5 immunohistochemistry. The peptidergic IENF were
determined by double immunofluorescence using anti-PGP9.5 and antibodies against
tropomyosin-receptor-kinase (Trk) A. We observed a significant increase in
PGP9.5-positive IENFD at 8 and 10 weeks of age. Similarly, Trk A-positive
peptidergic IENF, which also express substance P and calcitonin gene related
peptide in db/db mice, were observed to be elevated from 1.5 to 2 fold over
controls. This upregulation ended at 16 weeks of age, in accordance with the
reduction of mechanical allodynia. Anti-NGF treatment significantly inhibited
the upregulation of peptidergic IENFD during the period of mechanical allodynia,
suggesting that increased neurotrophism may mediate this phenomenon. In
addition, SB203580, an inhibitor of p38, blocked the increase in peptidergic
IENFD in db/db mice. The current results suggest that peptidergic IENFD could be
a potential diagnostic indicator for PDN in type 2 diabetes. Furthermore, the
inhibition of NGF-p38 signaling could be a potential therapeutic strategy for
treating this painful condition.


Investigators with authorship
NameInstitution
Eva FeldmanUniversity of Michigan

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