Glial cell line-derived neurotrophic factor normalizes neurochemical changes in injured dorsal root ganglion neurons and prevents the expression of experimental neuropathic pain

R. Wang, W. Guo, M. H. Ossipov, T. W. Vanderah, F. Porreca, J. Lai

Research output: Contribution to journalArticle

134 Scopus citations

Abstract

Glial cell line-derived neurotrophic factor (GDNF) is necessary for the development of sensory neurons, and appears to be critical for the survival of dorsal root ganglion (DRG) cells that bind the lectin IB4. Intrathecal infusion of GDNF has been shown to prevent and reverse the behavioral expression of experimental neuropathic pain arising from injury to spinal nerves. This effect of GDNF has been attributed to a blockade of the expression of the voltage gated, tetrodotoxin-sensitive sodium channel subtype, NaV1.3, in the injured DRG. Here we report that GDNF given intrathecally via osmotic-pump to nerve-injured rats (L5/L6 spinal nerve ligation) prevented the changes in a variety of neurochemical markers in the DRG upon injury. They include a loss of binding of IB4, downregulation of the purinergic receptor P2X3, upregulation of galanin and neuropeptide Y immunoreactivity in large diameter DRG cells, and expression of the transcription factor ATF3. GDNF infusion concomitantly prevented the development of spinal nerve ligation-induced tactile hypersensitivity and thermal hyperalgesia. These observations suggest that high dose, exogenous GDNF has a broad neuroprotective role in injured primary afferent. The receptor(s) that mediates these effects of GDNF is not known. GDNF's ability to block neuropathic pain states is not likely to be specific to NaV1.3 expression.

Original languageEnglish (US)
Pages (from-to)815-824
Number of pages10
JournalNeuroscience
Volume121
Issue number3
DOIs
StatePublished - Oct 15 2003

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Keywords

  • AKT
  • ATF3
  • Activating transcription factor 3
  • DRG
  • Dorsal root ganglion
  • FITC
  • Fluorescein isothiocyanate
  • GDNF
  • Nerve injury
  • Neuroprotection
  • Neurotrophic factor
  • Primary afferent
  • Sensory neurons
  • akt proto-oncogene protein/protein kinase B

ASJC Scopus subject areas

  • Neuroscience(all)

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