Brain-derived neurotrophic factor-activated astrocytes produce mechanical allodynia in neuropathic pain

Neuroscience. 2011 Dec 29:199:452-60. doi: 10.1016/j.neuroscience.2011.10.017. Epub 2011 Oct 20.

Abstract

Neuropathic pain management is challenging for physicians and a vexing problem for basic researchers. Recent studies reveal that activated spinal astrocytes may play a vital role in nerve injury-induced neuropathic pain, although the mechanisms are not fully understood. We have found increased glial fibrillary acidic protein (GFAP) expression, a hallmark of reactive gliosis, and elevated brain-derived neurotrophic factor (BDNF) expression in the dorsal horn in a rat model of allodynia induced by spinal nerve ligation (SNL). The high GFAP expression and mechanical allodynia that SNL induces were prevented by the intrathecal injection of the BDNF-sequestering fusion protein TrkB/Fc. Additionally, mechanical allodynia and GFAP overexpression was induced by the spinal administration of exogenous BDNF to naive rats, and exogenous BDNF given together with fluorocitrate, an astrocytic metabolism inhibitor, inhibited allodynia and GFAP upregulation. Exogenous BDNF also activated the astrocytes directly when tested in vitro. Furthermore, intrathecal administration of BDNF-stimulated astrocytes also induced mechanical allodynia in naive rats. All of these results indicate that astrocytes activated by BDNF might contribute to mechanical allodynia development in neuropathic pain in rats.

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Blotting, Western
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cell Separation
  • Disease Models, Animal
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Glial Fibrillary Acidic Protein / metabolism
  • Hyperalgesia / metabolism*
  • Ligation
  • Male
  • Neuralgia / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Nerves / injuries
  • Spinal Nerves / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • Glial Fibrillary Acidic Protein