Abstract
Glial cell line-derived neurotrophic factor (GDNF), a survival-promoting factor for
a subset of nociceptive small-diameter neurons, has been shown to exert analgesic
effects on neuropathic pain. However, its detailed mechanisms of action are still
unknown. In the present study, we investigated the site-specific analgesic effects
of GDNF in the neuropathic pain state using lentiviral vector-mediated GDNF overexpression
in mice with left fifth lumbar (L5) spinal nerve ligation (SNL) as a neuropathic pain
model. A lentiviral vector expressing both GDNF and enhanced green fluorescent protein
(EGFP) was constructed and injected into the left dorsal spinal cord, uninjured fourth
lumbar (L4) dorsal root ganglion (DRG), injured L5 DRG, or plantar skin of mice. In
SNL mice, injection of the GDNF-EGFP-expressing lentivirus into the dorsal spinal
cord or uninjured L4 DRG partially but significantly reduced the mechanical allodynia
in association with an increase in GDNF protein expression in each virus injection
site, whereas injection into the injured L5 DRG or plantar skin had no effects. These
results suggest that GDNF exerts its analgesic effects in the neuropathic pain state
by acting on the central terminals of uninjured DRG neurons and/or on the spinal cells
targeted by the uninjured DRG neurons.
Perspective
This article shows that GDNF exerts its analgesic effects on neuropathic pain by acting
on the central terminals of uninjured DRG neurons and/or on the spinal cells targeted
by these neurons. Therefore, research focusing on these GDNF-dependent neurons in
the uninjured DRG would provide a new strategy for treating neuropathic pain.
Key words
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Article info
Publication history
Published online: June 20, 2011
Accepted:
April 4,
2011
Received in revised form:
February 28,
2011
Received:
November 12,
2010
Footnotes
Supported by a Grant-in-Aid for Encouragement of Young Scientists (B) (22791457 to A.S.) from the Japan Society for the Promotion of Science and a grant (S0801035 to H.S.) from the Ministry of Education, Culture, Sports, Science and Technology, Japan.
Identification
Copyright
© 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.
