title: N-Acetyl-l-Cysteine Attenuates Ischemia/Reperfusion Injury-Induced Allodynia and N-Methyl-d-Aspartate Receptor Activation in Rats.
abstract: BACKGROUND
  Although reactive oxygen species (ROS) are believed to be involved in pathogenic mechanisms that underlie complex regional pain syndrome type I (CRPS-I), the role of ROS in the central mechanism of CRPS is not fully understood.
  
  
  OBJECTIVE
  In this study we investigated whether ROS scavenger N-acetyl-l-cysteine (NAC) was capable of attenuating mechanical allodynia and whether pain was decreased through modulating N-methyl-d-aspartate (NMDA) receptor activation in a chronic postischemia pain (CPIP) animal model that mimics the symptoms of CRPS-I.
  
  
  METHODS
  Thirty male Sprague-Dawley rats were randomly allocated to 5 different groups: (1) sham rats and CPIP rats treated with (2) vehicle; (3) NAC 30 mg/kg; (4) NAC 100 mg/kg; and (5) NAC 300 mg/kg intraperitoneally at 15 minutes before reperfusion. CPIP was generated after a 3-hour ischemia/reperfusion injury on the hind limb using a tight fitting O-ring. Then, mechanical paw-withdrawal thresholds to von Frey stimuli were assessed before ischemia (baseline), at 4 hours; 1, 3, and 5 days; and 1, 2, 3, and 4 weeks after reperfusion. Another set of 5 animal groups in the same categories was used to determine phosphorylated NMDA receptor 1 subunit (pNR1) immunoreactivity in the ipsilateral L4/6 spinal cord at 3 days after reperfusion.
  
  
  RESULTS
  The sham group showed no significant difference in pain thresholds over 4 weeks. With NAC treatment, the pain thresholds measured after reperfusion increased significantly, and this increase lasted 4 weeks after reperfusion compared with the vehicle group (P < 0.01 on the ipsilateral side and P < 0.05 on the contralateral side). The relative density of pNR1 at 3 days after reperfusion in NAC-treated rats decreased significantly compared with that of the vehicle group (all, P < 0.001). The NAC dose was significantly correlated not only with paw-withdrawal threshold (ρ = 0.979; P < 0.001) but also with the relative density of pNR1 (ρ = -0.875; P < 0.001).
  
  
  CONCLUSIONS
  NAC, administered during the pre-reperfusion period, had a long-term antiallodynic effect through the attenuation of NMDA receptor phosphorylation, leading to central sensitization.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Kyungpook National University School of Medicine, Jung gu, Daegu, Republic of Korea.
authors.forename: Kyung-Hwa
authors.initials: KH
authors.lastname: Kwak
authors.affiliation: Department of Anesthesiology and Pain Medicine, Kyungpook National University School of Medicine, Jung gu, Daegu, Republic of Korea.
authors.forename: Dong Gun
authors.initials: DG
authors.lastname: Lim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Kyungpook National University School of Medicine, Jung gu, Daegu, Republic of Korea.
authors.forename: Woon Yi
authors.initials: WY
authors.lastname: Baek
keywords: NAC; NMDA receptor activation; central sensitization; ischemia/reperfusion injury; pain; reactive oxygen species