Effect of N-acetylcysteine on the spinal-cord glutathione system and nitric-oxide metabolites in rats with neuropathic pain

Neurosci Lett. 2014 May 21:569:163-8. doi: 10.1016/j.neulet.2014.03.063. Epub 2014 Apr 3.

Abstract

Since N-acetylcysteine (NAC) is a donor of cysteine, we studied the relationship between NAC and concentration of oxidized and reduced glutathione (GSH/GSSG ratio), and glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities in the lumbosacral spinal cord of rats with chronic constriction injury (CCI) of the sciatic nerve that received NAC (150mg/kg/day, i.p.) or 0.9% saline solution for 3 or 10 days. Hydrogen peroxide (H2O2) and nitric-oxide (NO) metabolites were also measured. Von Frey hair and hot-plate tests showed hyperalgesia at day 1 in CCI rats. Hyperalgesia persisted at all other times in saline-treated CCI rats, but returned to pre-injury values in NAC-treated CCI rats after 3 postoperative days. GST activity and the GSH/GSSG ratio increased in saline-treated CCI rats, while the NAC treatment increased GST and GPx activities at day 10, with no significant change in the GSH/GSSG ratio. NAC treatment did not affect H2O2 levels, but it reduced NO metabolites in CCI rats 3 days after the surgery. Thus, the anti-hyperalgesic effect of NAC appears not to involve its action as a cysteine precursor for GSH synthesis, but involves a decrease in NO.

Keywords: Chronic constriction; Glutathione peroxidase; Glutathione-S-transferase; Hydrogen peroxide; Oxidized and reduced glutathione; Sciatic nerve.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology*
  • Analgesics / pharmacology*
  • Animals
  • Constriction, Pathologic
  • Glutathione / metabolism*
  • Glutathione Peroxidase / metabolism*
  • Glutathione Transferase / metabolism*
  • Hot Temperature
  • Hydrogen Peroxide / metabolism
  • Hyperalgesia / physiopathology
  • Lumbosacral Region
  • Male
  • Neuralgia / metabolism*
  • Neuralgia / physiopathology
  • Nitric Oxide / metabolism
  • Physical Stimulation
  • Rats, Wistar
  • Sciatic Nerve / injuries
  • Spinal Cord / drug effects*
  • Spinal Cord / metabolism
  • Touch

Substances

  • Analgesics
  • Nitric Oxide
  • Hydrogen Peroxide
  • Glutathione Peroxidase
  • Glutathione Transferase
  • Glutathione
  • Acetylcysteine