HSV-mediated gene transfer of the glial cell-derived neurotrophic factor provides an antiallodynic effect on neuropathic pain

Shuanglin Hao, Marina Mata, Darren Wolfe, Shaohua Huang, Joseph C. Glorioso, David J. Fink

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

Neuropathic pain is a difficult clinical problem that is often refractory to medical management. Glial-derived neurotrophic factor (GDNF) administered intrathecally has been shown to prevent or reduce pain in an animal model of neuropathic pain, but cannot be delivered in the required doses to treat human pain. We have previously demonstrated that peripheral subcutaneous inoculation of a replication-incompetent herpes simplex virus (HSV)-based vector can be used to transduce neurons of the dorsal root ganglion. To examine whether HSV-mediated expression of GDNF could be used to ameliorate neuropathic pain, we constructed a replication-incompetent HSV vector expressing GDNF. Subcutaneous inoculation of the vector 1 week after spinal nerve ligation resulted in a continuous antiallodynic effect that was maintained for 3-4 weeks. Reinoculation of the vector reestablished the antiallodynic effect with a magnitude that was at least equivalent to the initial effect. Vector-mediated GDNF expression blocked the nonnoxious touch-induced increase in c-fos expression in dorsal horn characteristic of the painful state. Gene transfer to produce a trophic factor offers a novel approach to the treatment of neuropathic pain that may be appropriate for human therapy.

Original languageEnglish (US)
Pages (from-to)367-375
Number of pages9
JournalMolecular Therapy
Volume8
Issue number3
DOIs
StatePublished - Sep 1 2003
Externally publishedYes

Keywords

  • GDNF
  • Gene therapy
  • HSV
  • Pain

ASJC Scopus subject areas

  • Molecular Biology

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