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Reversal of neurochemical changes and pain-related behavior in a model of neuropathic pain using modified lentiviral vectors expressing GDNF

Pezet, S ; Krzyzanowska, A ; Wong, LF ; Grist, J ; Mazarakis, ND ; Georgievska, Biljana LU and McMahon, SB (2006) In Molecular Therapy 13(6). p.1101-1109
Abstract
In this study, we evaluated the possible use of lentiviral vectors in the treatment of neuropathic pain. We chose to administer GDNF-expressing vectors because of the known beneficial effect of this trophic factor in alleviation of neuropathic pain in adult rodents. Lentiviral vectors expressing either GDNF or control, green fluorescent protein or beta-galactosidase, were injected unilaterally into the spinal dorsal horn 5 weeks before a spinal nerve ligation was induced (or sham surgery for the controls). We observed that intraspinally administered lentiviral vectors resulted in a large and sustained expression of transgenes in both neurons and glial cells. Injection of GDNF-expressing viral vectors induced a significant reduction of... (More)
In this study, we evaluated the possible use of lentiviral vectors in the treatment of neuropathic pain. We chose to administer GDNF-expressing vectors because of the known beneficial effect of this trophic factor in alleviation of neuropathic pain in adult rodents. Lentiviral vectors expressing either GDNF or control, green fluorescent protein or beta-galactosidase, were injected unilaterally into the spinal dorsal horn 5 weeks before a spinal nerve ligation was induced (or sham surgery for the controls). We observed that intraspinally administered lentiviral vectors resulted in a large and sustained expression of transgenes in both neurons and glial cells. Injection of GDNF-expressing viral vectors induced a significant reduction of ATF-3 up-regulation and 1134 down-regulation in damaged DRG neurons. In addition, it produced a partial but significant reversal of thermal and mechanical hyperalgesia observed following the spinal nerve ligation. In conclusion, our study suggests that lentiviral vectors are efficient tools to induce a marked and sustained expression of trophic factors in specific areas of the CNS and can, even if with some limitations, be efficient in the treatment of neuropathic pain. (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ATF-3, trophic factor, survival, neuroprotection, spinal cord, IB4
in
Molecular Therapy
volume
13
issue
6
pages
1101 - 1109
publisher
Nature Publishing Group
external identifiers
  • pmid:16504588
  • wos:000238402000011
  • scopus:33746234869
  • pmid:16504588
ISSN
1525-0024
DOI
10.1016/j.ymthe.2005.11.026
language
English
LU publication?
yes
id
308200dd-17b7-478e-bd09-87c7d75ece34 (old id 405929)
date added to LUP
2016-04-01 11:44:10
date last changed
2021-04-06 01:27:07
@article{308200dd-17b7-478e-bd09-87c7d75ece34,
  abstract     = {In this study, we evaluated the possible use of lentiviral vectors in the treatment of neuropathic pain. We chose to administer GDNF-expressing vectors because of the known beneficial effect of this trophic factor in alleviation of neuropathic pain in adult rodents. Lentiviral vectors expressing either GDNF or control, green fluorescent protein or beta-galactosidase, were injected unilaterally into the spinal dorsal horn 5 weeks before a spinal nerve ligation was induced (or sham surgery for the controls). We observed that intraspinally administered lentiviral vectors resulted in a large and sustained expression of transgenes in both neurons and glial cells. Injection of GDNF-expressing viral vectors induced a significant reduction of ATF-3 up-regulation and 1134 down-regulation in damaged DRG neurons. In addition, it produced a partial but significant reversal of thermal and mechanical hyperalgesia observed following the spinal nerve ligation. In conclusion, our study suggests that lentiviral vectors are efficient tools to induce a marked and sustained expression of trophic factors in specific areas of the CNS and can, even if with some limitations, be efficient in the treatment of neuropathic pain.},
  author       = {Pezet, S and Krzyzanowska, A and Wong, LF and Grist, J and Mazarakis, ND and Georgievska, Biljana and McMahon, SB},
  issn         = {1525-0024},
  language     = {eng},
  number       = {6},
  pages        = {1101--1109},
  publisher    = {Nature Publishing Group},
  series       = {Molecular Therapy},
  title        = {Reversal of neurochemical changes and pain-related behavior in a model of neuropathic pain using modified lentiviral vectors expressing GDNF},
  url          = {http://dx.doi.org/10.1016/j.ymthe.2005.11.026},
  doi          = {10.1016/j.ymthe.2005.11.026},
  volume       = {13},
  year         = {2006},
}