Brain-derived neurotrophic factor redistribution in the dorsal root ganglia correlates with neuropathic pain inhibition after resiniferatoxin treatment

Gabriel C. Tender, Yuan Yuan Li, Jian Guo Cui

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Background context: Brain-derived neurotrophic factor (BDNF) and its cognate receptor, the tyrosine kinase B (TrkB), are normally expressed in neurons and implicated in multiple pathological conditions. Brain-derived neurotrophic factor is produced in the central nervous system microglia in response to noxious stimuli and appear to potentiate central sensitization. Resiniferatoxin (RTX) is an excitotoxic agonist of the vanilloid receptor 1 (VR1), a cation channel protein considered an integrator for nociception. Resiniferatoxin, administered into the dorsal root ganglia (DRG), selectively eliminates the VR1-positive neurons and improves tactile allodynia in a neuropathic pain rat model. Purpose: The goal of the present study was to evaluate the role of BDNF in RTX-induced neuropathic pain suppression. Study design: The study design was a sciatic nerve injury animal model with intraganglionic RTX injection. Methods: Resiniferatoxin was injected into the DRG of the L3-L6 spinal nerves after the rats displayed tactile allodynia and thermal hyperalgesia produced by a photochemical injury to the sciatic nerve. Behavioral testing and immunohistochemical and mRNA analysis of the DRG were performed to determine BDNF's role in pain modulation. Results: Brain-derived neurotrophic factor expression in the DRG of neuropathic rats was upregulated in the small- and medium-size neurons, whereas the upregulation was observed in the large-size neurons of non-neuropathic rat DRG. A high-dose RTX injection in the DRG of neuropathic rats led to elimination of both thermal hyperalgesia and tactile allodynia and also upregulated BDNF in the large-size neurons, similar to the nonallodynic rats. Tyrosine kinase B changes mirrored the BDNF ones. Conclusion: Resiniferatoxin injection in the DRG of neuropathic rats upregulates BDNF expression in the same pattern as in the large-size neurons of non-neuropathic rats. Therefore, BDNF upregulation may have pain suppressive effects. These effects are likely mediated by TrkB.

Original languageEnglish (US)
Pages (from-to)715-720
Number of pages6
JournalSpine Journal
Volume10
Issue number8
DOIs
StatePublished - Aug 1 2010

Keywords

  • Brain-derived neurotrophic factor
  • Dorsal root ganglia
  • Neuropathic pain
  • Resiniferatoxin
  • Vanilloid receptor 1

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

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