title: Role of oxidative stress in pathophysiology of peripheral neuropathy and modulation by N-acetyl-L-cysteine in rats.
abstract: OBJECTIVE
  The objectives of this study were to examine the role of reactive oxygen species and oxidative stress in peripheral neuropathy and behavioural pain responses in experimentally induced chronic constriction injury (CCI) of sciatic nerve of rat. Effect of N-acetyl-L-cysteine (NAC) administered intraperitoneally, was also investigated on CCI-induced neuropathic pain in rats.
  
  
  METHODS
  Neuropathy was induced by CCI of the right sciatic nerve in ketamine anaesthetized rats. Effect of intraperitoneally administered NAC in rats was also investigated using nociceptive behavioural tests. Malondialdehyde, an index of oxidative stress and antioxidant enzymes was also estimated in ligated sciatic nerve.
  
  
  RESULTS
  Behavioural tests, mechanical, thermal and cold stimuli confirmed the development of neuropathic pain after the CCI. The malondialdehyde levels of ligated sciatic nerves were significantly increased compared to non-ligated sciatic nerves (sham operated). The antioxidant enzyme reduced, glutathione was inhibited, while superoxide dismutase increased. However, catalase remained unaffected in the injured sciatic nerves. Intraperitoneal administration of NAC resulted in significant reduction of hyperalgesia in CCI-induced neuropathic rats.
  
  
  CONCLUSIONS
  This study identifies antioxidants superoxide dismutase and reduced glutathione, and oxidative stress as important determinants of neuropathological and behavioural consequences of CCI-induced neuropathy, and NAC may be a potential candidate for alleviation of neuropathic pain.
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar-243 122 UP, India.
authors.forename: Ajit K
authors.initials: AK
authors.lastname: Naik
authors.forename: Surendra K
authors.initials: SK
authors.lastname: Tandan
authors.forename: Shailesh P
authors.initials: SP
authors.lastname: Dudhgaonkar
authors.forename: Sachin H
authors.initials: SH
authors.lastname: Jadhav
authors.forename: Meena
authors.initials: M
authors.lastname: Kataria
authors.forename: V Ravi
authors.initials: VR
authors.lastname: Prakash
authors.forename: Dinesh
authors.initials: D
authors.lastname: Kumar
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D005978:Glutathione / Q000378:metabolism; D008026:Ligation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010147:Pain Measurement / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D005978:Glutathione; D000111:Acetylcysteine