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

S Pezet, A Krzyzanowska, LF Wong, J Grist, ND Mazarakis, B Georgievka, SB McMahon

Research output: Contribution to journalArticle (Academic Journal)peer-review

53 Citations (Scopus)

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 IB4 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.
Translated title of the contributionReversal of neurochemical changes and pain-related behavior in a model of neuropathic pain using modified lentiviral vectors expressing GDNF
Original languageEnglish
Pages (from-to)1101 - 1109
Number of pages9
JournalMolecular Therapy
Volume13 (6)
DOIs
Publication statusPublished - Jun 2006

Bibliographical note

Publisher: Nature Publishing Group

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