title: Superoxide and Nitric Oxide Involvement in Enhancing of N-methyl-D-aspartate Receptor-Mediated Central Sensitization in the Chronic Post-ischemia Pain Model.
abstract: BACKGROUND
  Recent studies indicate that reactive oxygen species (ROS) are involved in persistent pain, including neuropathic and inflammatory pain. Since the data suggest that ROS are involved in central sensitization, the present study examines the levels of activated N-methyl-D-aspartate (NMDA) receptors in the dorsal horn after an exogenous supply of three antioxidants in rats with chronic post-ischemia pain (CPIP). This serves as an animal model of complex regional pain syndrome type-I induced by hindpaw ischemia/reperfusion injury.
  
  
  METHODS
  The application of tight-fitting O-rings for a period of three hours produced CPIP in male Sprague-Dawley rats. Allopurinol 4 mg/kg, allopurinol 40 mg/kg, superoxide dismutase (SOD) 4,000 U/kg, N-nitro-L-arginine methyl ester (L-NAME) 10 mg/kg and SOD 4,000 U/kg plus L-NAME 10 mg/kg were administered intraperitoneally just after O-ring application and on the first and second days after reperfusion. Mechanical allodynia was measured, and activation of the NMDA receptor subunit 1 (pNR1) of the lumbar spinal cord (L4-L6) was analyzed by the Western blot three days after reperfusion.
  
  
  RESULTS
  Allopurinol reduced mechanical allodynia and attenuated the enhancement of spinal pNR1 expression in CPIP rats. SOD and L-NAME also blocked spinal pNR1 in accordance with the reduced mechanical allodynia in rats with CPIP.
  
  
  CONCLUSIONS
  The present data suggest the contribution of superoxide, produced via xanthine oxidase, and the participation of superoxide and nitric oxide as a precursor of peroxynitrite in NMDA mediated central sensitization. Finally, the findings support a therapeutic potential for the manipulation of superoxide and nitric oxide in ischemia/reperfusion related pain conditions.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Tae Ha
authors.initials: TH
authors.lastname: Ryu
authors.forename: Kyung Young
authors.initials: KY
authors.lastname: Jung
authors.forename: Mi Jin
authors.initials: MJ
authors.lastname: Ha
authors.forename: Kyung Hwa
authors.initials: KH
authors.lastname: Kwak
authors.forename: Dong Gun
authors.initials: DG
authors.lastname: Lim
authors.forename: Jung Gil
authors.initials: JG
authors.lastname: Hong