Reactive oxygen species in rats with chronic post-ischemia pain.
BACKGROUND
An emerging theme in the study of the pathophysiology of persistent pain is the role of reactive oxygen species (ROS). In the present study, we examined the hypothesis that the exogenous supply of antioxidant drugs during peri-reperfusion would attenuate pain induced by ischemia/reperfusion (IR) injury. We investigated the analgesic effects of three antioxidants administered during peri-reperfusion using an animal model of complex regional pain syndrome-type I consisting of chronic post-ischemia pain (CPIP) of the hind paw.


METHODS
Application of a tight-fitting tourniquet for a period of 3 h produced CPIP in male Sprague-Dawley rats. Low-dose allopurinol (4 mg/kg), high-dose allopurinol (40 mg/kg), superoxide dismutase (SOD, 4000 U/kg), N-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg), or SOD (4000 U/kg)+L-NAME (10 mg/kg) was administered intraperitoneally just after tourniquet application and at 1 and 2 days after reperfusion for 3 days. The effects of antioxidants in rats were investigated using mechanical and cold stimuli. Each group consisted of seven rats.


RESULTS
Allopurinol caused significant alleviation in mechanical and cold allodynia for a period of 4 weeks in rats with CPIP. Both SOD and L-NAME, which were used to investigate the roles of superoxide (O2(-)) and nitric oxide (NO) in pain, also attenuated neuropathic-like pain symptoms in rats for 4 weeks.


CONCLUSIONS
Our findings suggest that O2(-) and NO mediate IR injury-induced chronic pain, and that ROS scavengers administered during the peri-reperfusion period have long-term analgesic effects.
Kwak
K H
KH
Department of Anesthesiology and Pain medicine, School of Medicine, Kyungpook National University, Daegu, Korea.
Han
C G
CG
Lee
S H
SH
Jeon
Y
Y
Park
S S
SS
Kim
S O
SO
Baek
W Y
WY
Hong
J G
JG
Lim
D G
DG
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002908:Chronic Disease; D003080:Cold Temperature; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D007511:Ischemia / Q000150:complications*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D010146:Pain / Q000209:etiology / Q000378:metabolism; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000150:complications; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D000493:Allopurinol; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D019331:NG-Nitroarginine Methyl Ester