Peripherally delivered glutamic acid decarboxylase gene therapy for spinal cord injury pain

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

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Neuropathic pain after spinal cord injury (SCI) represents a difficult problem that is commonly refractory to conventional medical management. To determine if spinal release of γ-amino butyric acid (GABA) could reduce below-level central neuropathic pain after SCI, we constructed a replication-incompetent herpes simplex virus (HSV)-based vector encoding one isoform of human glutamic acid decarboxylase (GAD67). Dorsal root ganglion (DRG) neurons transduced in vitro or in vivo by subcutaneous inoculation produced GAD and released GABA constitutively. T13 spinal cord hemisection resulted in central neuropathic pain manifested by mechanical allodynia and thermal hyperalgesia. Subcutaneous inoculation of the vector into both feet reduced both manifestations of below-level SCI pain; the vector-mediated effect was partially reversed by intrathecal bicuculline or phaclofen at doses that did not affect thresholds in normal or injured uninoculated animals. Vector-mediated GABA release attenuated the increase in spinal calcitonin gene-related peptide immunoreactivity caused by cord hemisection. These results suggest that HSV-mediated gene transfer to DRG could be used to treat below-level central neuropathic pain after incomplete SCI.

Original languageEnglish
Pages (from-to)57-66
Number of pages10
JournalMolecular Therapy
Volume10
Issue number1
DOIs
StatePublished - Jul 1 2004
Externally publishedYes

Fingerprint

Glutamate Decarboxylase
Neuralgia
Spinal Cord Injuries
Genetic Therapy
Hyperalgesia
gamma-Aminobutyric Acid
Pain
Spinal Ganglia
Simplexvirus
Butyric Acid
Bicuculline
Calcitonin Gene-Related Peptide
Foot
Spinal Cord
Protein Isoforms
Neurons
Genes

Keywords

  • GABA
  • GAD
  • Gene therapy
  • HSV
  • Neuropathic pain
  • Spinal cord injury

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Peripherally delivered glutamic acid decarboxylase gene therapy for spinal cord injury pain. / Liu, Jun; Wolfe, Darren; Hao, Shuanglin; Huang, Shaohua; Glorioso, Joseph C.; Mata, Marina; Fink, David J.

In: Molecular Therapy, Vol. 10, No. 1, 01.07.2004, p. 57-66.

Research output: Contribution to journalArticle

Liu, Jun ; Wolfe, Darren ; Hao, Shuanglin ; Huang, Shaohua ; Glorioso, Joseph C. ; Mata, Marina ; Fink, David J. / Peripherally delivered glutamic acid decarboxylase gene therapy for spinal cord injury pain. In: Molecular Therapy. 2004 ; Vol. 10, No. 1. pp. 57-66.
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