Activation of astrocytes in the spinal cord contributes to the development of bilateral allodynia after peripheral nerve injury in rats

Brain Res. 2010 Dec 2:1363:72-80. doi: 10.1016/j.brainres.2010.09.105. Epub 2010 Oct 25.

Abstract

Activation of spinal cord microglia and astrocytes after peripheral nerve injury contributes to the development of behavioral hypersensitivity. Suppression of spinal cord glial activation attenuates the development of nerve injury-induced allodynia. The contribution of spinal cord glia to existing allodynia, however, is not known. We investigated whether intrathecally administered propentofylline, a glial inhibitor, reverses existing allodynia after nerve injury. Male Sprague-Dawley rats underwent L5 spinal nerve transection, and mechanical allodynia was assessed by measuring hind paw withdrawal thresholds bilaterally using von Frey filaments. Rats received either saline or propentofylline (1, 3, and 10 μg/d) for 7 days (days 0-7) by intrathecal infusion with an osmotic minipump. Other groups of rats received either intrathecal infusion of saline or propentofylline (10 μg/d) for 7 days on days 14-21 or 60-67 after surgery. After completing the intrathecal infusion, lumbar spinal cord sections were assessed for immunostaining of astrocytic glial fibrillary acidic protein and microglial OX-42. Propentofylline infusion on days 0-7 suppressed development of allodynia in both the ipsilateral and contralateral hind paws in a dose-dependent manner. Propentofylline treatment on days 14-21 or 60-67 did not reverse existing allodynia. Propentofylline infusion (10 μg/d) inhibited astrocytic activation bilaterally on days 0-7, 14-21, and 60-67 and inhibited microglial activation on days 14-21 but not on days 0-7 and 60-67. These results suggest that activation of spinal glia, especially astrocytes, dominantly contributes to the development of neuropathic pain and also to mirror-image pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / drug effects
  • Astrocytes / physiology*
  • Dose-Response Relationship, Drug
  • Hyperalgesia / drug therapy
  • Hyperalgesia / physiopathology*
  • Injections, Spinal
  • Lumbar Vertebrae
  • Male
  • Microglia / drug effects
  • Microglia / physiology
  • Neuralgia / drug therapy
  • Neuralgia / physiopathology*
  • Neuroprotective Agents / pharmacology
  • Pain Threshold / drug effects
  • Pain Threshold / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord / physiopathology*
  • Spinal Nerves / injuries*
  • Spinal Nerves / physiopathology
  • Xanthines / pharmacology

Substances

  • Neuroprotective Agents
  • Xanthines
  • propentofylline