Role of oxidative stress in pathophysiology of peripheral neuropathy and modulation by N-acetyl-L-cysteine in rats.
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.
Naik
Ajit K
AK
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar-243 122 UP, India.
Tandan
Surendra K
SK
Dudhgaonkar
Shailesh P
SP
Jadhav
Sachin H
SH
Kataria
Meena
M
Prakash
V Ravi
VR
Kumar
Dinesh
D
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
D015415:Biomarkers; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D005978:Glutathione; D000111:Acetylcysteine