Reactive oxygen species (ROS) play an important role in a rat model of neuropathic pain.
Reactive oxygen species (ROS) are free radicals produced in biological systems that are involved in various degenerative brain diseases. The present study tests the hypothesis that ROS also play an important role in neuropathic pain. In the rat spinal nerve ligation (SNL) model of neuropathic pain, mechanical allodynia develops fully 3 days after nerve ligation and persists for many weeks. Systemic injection of a ROS scavenger, phenyl-N-tert-butylnitrone (PBN), relieves SNL-induced mechanical allodynia in a dose-dependent manner. Repeated injections cause no development of tolerance or no loss of potency. Preemptive treatment with PBN is also effective in preventing full development of neuropathic pain behavior. Systemic injection was mimicked by intrathecal injection with a little less efficacy, while intracerebroventricular administration produced a much smaller effect. These data suggest that PBN exerts its anti-allodynic action mainly by spinal mechanisms. Systemic treatment with other spin-trap reagents, 5,5-dimethylpyrroline-N-oxide and nitrosobenzene, showed similar analgesic effects, suggesting that ROS are critically involved in the development and maintenance of neuropathic pain. Thus this study suggests that systemic administration of non-toxic doses of free radical scavengers could be useful for treatment of neuropathic pain.
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1069, USA.
Hee Kee
HK
Kim
Soon Kwon
SK
Park
Jun-Li
JL
Zhou
Giulio
G
Taglialatela
Kyungsoon
K
Chung
Richard E
RE
Coggeshall
Jin Mo
JM
Chung
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D003497:Cyclic N-Oxides; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000494:pharmacology; D008026:Ligation; D008297:Male; D009437:Neuralgia / Q000188:drug therapy / Q000378:metabolism*; D009589:Nitrogen Oxides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013127:Spinal Nerves
D000700:Analgesics; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D009589:Nitrogen Oxides; D017382:Reactive Oxygen Species; C029217:phenyl-N-tert-butylnitrone