title: Spinal mitochondrial-derived ROS contributes to remifentanil-induced postoperative hyperalgesia via modulating NMDA receptor in rats.
abstract: BACKGROUND
  Activation of N-methyl-d-aspartate (NMDA) receptor by reactive oxygen species (ROS) in the spinal cord plays an important role in the development of hyperalgesia in several neuropathic pain models. The study examined the involvement of ROS-NMDA signaling pathway in remifentanil-induced postoperative hyperalgesia.
  
  
  METHODS
  Nociceptive responses were measured by paw withdrawal mechanical threshold (PWT) and paw withdrawal thermal latency (PWL) before and up to day 5 after remifentanil infusion. Spinal delivery of MitoSOX red was performed to detect mitochondrial ROS. Changes in expression of NMDA receptor subunits (NR1 and NR2B) in the spinal cord were analyzed by immunofluorescence and Western blotting. Intraperitoneal injection of phenyl-N-tert-butylnitrone (PBN), a non-selective ROS scavenger, was administrated to investigate the role of ROS in remifentanil-induced postoperative hyperalgesia.
  
  
  RESULTS
  Intraoperative infusion of remifentanil induced postoperative mechanical allodynia and thermal hyperalgesia. ROS production, phosphorylated NR1 and NR2B subunits of NMDA receptor were found to be significantly increased in the spinal dorsal horn after intraoperative remifentanil infusion. However, remifentanil-induced postoperative hyperalgesia was suppressed by pretreatment of PBN. In addition, reduction of ROS by PBN prevented enhanced phosphorylation of NR1 and NR2B subunits.
  
  
  CONCLUSIONS
  These findings indicated that ROS-dependent activation of NMDA receptor in the spinal cord might be a potential mechanism underlying remifentanil-induced postoperative hyperalgesia.
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Department of Anesthesiology, Affiliated Tumor Hospital, Guangxi Medical University, Nanning, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Shi-Ying
authors.initials: SY
authors.lastname: Yang
authors.affiliation: Neurobiology Research Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Neurobiology Research Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: chenyusysu@hotmail.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects*; D018686:Anesthetics, Intravenous / Q000009:adverse effects*; D000818:Animals; D003497:Cyclic N-Oxides / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D017288:Pain Threshold; D010149:Postoperative Pain / Q000139:chemically induced / Q000378:metabolism*; D010766:Phosphorylation; D010880:Piperidines / Q000009:adverse effects*; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D000077208:Remifentanil; D013116:Spinal Cord / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; D018686:Anesthetics, Intravenous; D003497:Cyclic N-Oxides; C409466:NR1 NMDA receptor; C121001:NR2B NMDA receptor; D010880:Piperidines; D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate; C029217:phenyl-N-tert-butylnitrone; D000077208:Remifentanil
keywords: Hyperalgesia; Mitochondrial; NMDA receptor; ROS; Remifentanil