| Authors |
Hsinlin T Cheng, John M Hayes, Yu Hong and Eva L Feldman
|
| Submitted By |
Eva Feldman on 4/17/2009 |
| Status |
Published |
| Journal |
Journal of neuropathology and experimental neurology |
| Year |
2009 |
| Volume : Pages |
Not Specified : Not Specified |
| PubMed Reference |
19816194 |
| Abstract |
We reported previously that the C57BLKS db/db (db/db) mouse develops the
neuropathy of type 2 diabetes. In the current study, we demonstrate that the
db/db mouse develops transient mechanical allodynia at the early stage of
diabetes. We hypothesize that nerve growth factor (NGF) mediates the development
of mechanical allodynia in the db/db mouse. NGF, substance P (SP), and
calcitonin gene related peptide (CGRP) gene expression was upregulated in the
dorsal root ganglion (DRG) of db/db mice during the period of mechanical
allodynia. In parallel, there were increased numbers of small- to medium-sized
NGF-immunopositive DRG neurons in db/db mice in comparison with the control db+
mice. These neurons also expressed SP, suggesting that they mediated
nociception. The NGF expression in the hind paw skin was also increased in the
period of mechanical allodynia. This peripheral NGF upregulation was associated
with increased numbers of SP-positive intraepidermal nerve fibers (IENF). This
upregulation of NGF coincided with enhanced tropomyosin-related kinase (Trk) A
receptor phosphorylation in DRG. Finally, an antibody against NGF significantly
inhibited mechanical allodynia and SP expression in db/db mice. The current
findings provide evidence that inhibition of NGF action is a potential strategy
for treating painful diabetic neuropathy.
Key words: Diabetes; Neuropathy; Nerve Growth Factor; Pain; Substance P; Dorsal
Root Ganglion; Db/db mice
|
|
| Investigators with authorship |
| Name | Institution |
| Eva Feldman | University of Michigan |
|
