Protective effects of gabapentin on allodynia and alpha 2 delta 1-subunit of voltage-dependent calcium channel in spinal nerve-ligated rats

J Korean Med Sci. 2009 Feb;24(1):146-51. doi: 10.3346/jkms.2009.24.1.146. Epub 2009 Feb 28.

Abstract

This study was designed to determine whether early gabapentin treatment has a protective analgesic effect on neuropathic pain and compared its effect to the late treatment in a rat neuropathic model, and as the potential mechanism of protective action, the alpha(2)delta(1)-subunit of the voltage-dependent calcium channel (alpha(2)delta(1)-subunit) was evaluated in both sides of the L5 dorsal root ganglia (DRG). Neuropathic pain was induced in male Sprague-Dawley rats by a surgical ligation of left L5 nerve. For the early treatment group, rats were injected with gabapentin (100 mg/kg) intraperitoneally 15 min prior to surgery and then every 24 hr during postoperative day (POD) 1-4. For the late treatment group, the same dose of gabapentin was injected every 24 hr during POD 8-12. For the control group, L5 nerve was ligated but no gabapentin was administered. In the early treatment group, the development of allodynia was delayed up to POD 10, whereas allodynia was developed on POD 2 in the control and the late treatment group (p<0.05). The alpha(2)delta(1)-subunit was up-regulated in all groups, however, there was no difference in the level of the alpha(2)delta(1)-subunit among the three groups. These results suggest that early treatment with gabapentin offers some protection against neuropathic pain but it is unlikely that this action is mediated through modulation of the alpha(2)delta(1)-subunit in DRG.

Keywords: Alpha 2 Delta-1 Subunit; Calcium Channels; Gabapentin; Neuropathic Pain; Protective.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / administration & dosage
  • Amines / therapeutic use*
  • Analgesics / administration & dosage
  • Analgesics / therapeutic use*
  • Animals
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Calcium Channels, L-Type
  • Cyclohexanecarboxylic Acids / administration & dosage
  • Cyclohexanecarboxylic Acids / therapeutic use*
  • Disease Models, Animal
  • Gabapentin
  • Injections, Intraperitoneal
  • Ligation
  • Male
  • Neuralgia / drug therapy*
  • Neuralgia / metabolism
  • Pain Measurement
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Nerves / surgery
  • Up-Regulation
  • gamma-Aminobutyric Acid / administration & dosage
  • gamma-Aminobutyric Acid / therapeutic use*

Substances

  • Amines
  • Analgesics
  • Cacna2d1 protein, rat
  • Calcium Channels
  • Calcium Channels, L-Type
  • Cyclohexanecarboxylic Acids
  • Protein Subunits
  • gamma-Aminobutyric Acid
  • Gabapentin