Amelioration of chronic neuropathic pain after partial nerve injury by adeno-associated viral (AAV) vector-mediated over-expression of BDNF in the rat spinal cord

M. J. Eaton, B. Blits, M. J. Ruitenberg, J. Verhaagen, M. Oudega

Research output: Contribution to journalArticlepeer-review

123 Scopus citations

Abstract

Changing the levels of neurotrophins in the spinal cord micro-environment after nervous system injury has been proposed to recover normal function, such that behavioral response to peripheral stimuli does not lead to chronic pain. We have investigated the effects of recombinant adeno-associated viral (rAAV)-mediated over-expression of brain-derived neurotrophic factor (BDNF) in the spinal cord on chronic neuropathic pain after unilateral chronic constriction injury (CCI) of the sciatic nerve. The rAAV-BDNF vector was injected into the dorsal horn at the thirteenth thoracic spinal cord vertebra (L1 level) 1 week after CCI. Allodynia and hyperalgesia induced by CCI in the hindpaws were permanently reversed, beginning 1 week after vector injection, compared with a similar injection of a control rAAV-GFP vector (green fluorescent protein) or saline. In situ hybridization for BDNF demonstrated that both dorsal and ventral lumbar spinal neurons contained an intense signal for BDNF mRNA, at 1 to 8 weeks after vector injection. There was no similar BDNF mRNA over-expression associated with either injections of saline or rAAV-GFP. These data suggest that chronic neuropathic pain is sensitive to early spinal BDNF levels after partial nerve injury and that rAAV-mediated gene transfer could potentially be used to reverse chronic pain after nervous system injuries in humans.

Original languageEnglish (US)
Pages (from-to)1387-1395
Number of pages9
JournalGene Therapy
Volume9
Issue number20
DOIs
StatePublished - 2002

Keywords

  • Brain-derived neurotrophic factor
  • CCI
  • Nerve injury
  • Persistent pain
  • Virus-mediated gene transfer

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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