title: Tyrosine phosphorylation of the N-Methyl-D-Aspartate receptor 2B subunit in spinal cord contributes to remifentanil-induced postoperative hyperalgesia: the preventive effect of ketamine.
abstract: BACKGROUND
  Experimental and clinical studies showed that intraoperative infusion of remifentanil has been associated with postoperative hyperalgesia. Previous reports suggested that spinal N-methyl-D-aspartate (NMDA) receptors may contribute to the development and maintenance of opioid-induced hyperalgesia. In the present study, we used a rat model of postoperative pain to investigate the role of tyrosine phosphorylation of NMDA receptor 2B (NR2B) subunit in spinal cord in the postoperative hyperalgesia induced by remifentanil and the intervention of pretreatment with ketamine.
  
  
  RESULTS
  Intraoperative infusion of remifentanil (0.04 mg/kg, subcutaneous) significantly enhanced mechanical allodynia and thermal hyperalgesia induced by the plantar incision during the postoperative period (each lasting between 2 h and 48 h), which was attenuated by pretreatment with ketamine (10 mg/kg, subcutaneous). Correlated with the pain behavior changes, immunocytochemical and western blotting experiments in our study revealed that there was a marked increase in NR2B phosphorylation at Tyr1472 in the superficial dorsal horn after intraoperative infusion of remifentanil, which was attenuated by pretreatment with ketamine.
  
  
  CONCLUSIONS
  This study provides direct evidence that tyrosine phosphorylation of the NR2B at Tyr1472 in spinal dosal horn contributes to postoperative hyperalgesia induced by remifentanil and supports the potential therapeutic value of ketamine for improving postoperative hyperalgesia induced by remifentanil.
authors.affiliation: Department of Anesthesiology, Drum Tower Hospital, Medical Department of Nanjing University, Nanjing 210008, Jiangsu Province, China. yys982002@yahoo.com.cn
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Gu
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wu
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.forename: Songqin
authors.initials: S
authors.lastname: Cui
authors.forename: Zhengliang
authors.initials: Z
authors.lastname: Ma
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D018698:Glutamic Acid / Q000378:metabolism; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D018836:Inflammation Mediators / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism; D010149:Postoperative Pain / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D000077208:Remifentanil; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; D018836:Inflammation Mediators; C121001:NR2B NMDA receptor; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D014443:Tyrosine; D007649:Ketamine; D000077208:Remifentanil