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, Biljana Georgievska, SB McMahon

Research output: Contribution to journalArticlepeer-review

53 Citations (SciVal)

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.
Original languageEnglish
Pages (from-to)1101-1109
JournalMolecular Therapy
Volume13
Issue number6
DOIs
Publication statusPublished - 2006

Subject classification (UKÄ)

  • Medical Genetics

Keywords

  • ATF-3
  • trophic factor
  • survival
  • neuroprotection
  • spinal cord
  • IB4

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