Increased axonal regeneration and swellings in intraepidermal nerve fibers
characterize painful phenotypes of diabetic neuropathy.
Authors Cheng HT, Dauch JR, Porzio MT, Yanik BM, Hsieh W, Smith AG, Singleton JR,
Feldman EL
Submitted By Eva Feldman on 4/15/2014
Status Published
Journal The journal of pain : official journal of the American Pain Society
Year 2013
Date Published 9/1/2013
Volume : Pages 14 : 941 - 947
PubMed Reference 23685187
Abstract We examined changes in intraepidermal nerve fibers (IENFs) to differentiate
patients with diabetic neuropathy (DN) and diabetic neuropathic pain (DN-P) from
those with DN without pain (DN-NOP). Punch skin biopsies were collected from the
proximal thigh (PT) and distal leg (DL) of normal subjects, patients with type 2
diabetes without evidence of DN (DM), or DN-P and DN-NOP patients. Protein gene
product 9.5-positive (PGP+) immunohistochemistry was used to quantify total
IENF, and growth-associated protein 43 (GAP43) for regenerating IENF. Compared
to normal subjects and patients with type 2 diabetes without evidence of DN,
both DN-P and DN-NOP have reduced PGP+ IENF densities in DL and PT. Although
GAP43+ IENF densities were also reduced in DL for both DN-P and DN-NOP, the
GAP43+ IENF densities in PT of DN-P remained at the control levels. Higher
GAP43/PGP ratios were detected in DN-P compared to DN-NOP in the DL and PT. In
parallel, increased numbers of axonal swellings per PGP+ fiber (axonal
swelling/PGP) were detected in DN-P compared to normal subjects, patients with
type 2 diabetes without evidence of DN, and DN-NOP in the DL. These axonal
swellings were positive for tropomyosin-receptor-kinase A and substance P,
suggesting that they are associated with nociception.


Investigators with authorship
NameInstitution
Eva FeldmanUniversity of Michigan

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