title: Phosphorylated CaMKII levels increase in rat central nervous system after large-dose intravenous remifentanil.
abstract: BACKGROUND
  Postoperative remifentanil-induced pain sensitization is common, but its molecular mechanism remains unclear. Calcium/calmodulin-dependent protein kinase II (CaMKII) has been shown to have a critical role in morphine-induced hyperalgesia. This study was designed to determine how CaMKII phosphorylation and protein expression levels change in the central nervous system of rats with remifentanil-induced hyperalgesia.
  
  
  METHODS
  Male Sprague-Dawley® rats were exposed to large-dose (bolus of 6.0 µg/kg and 2.5 µg/kg/min for 2 hours) intravenous remifentanil to induce post-transfusion hyperalgesia. Levels of phosphorylated CaMKII (P-CaMKII) and total protein of CaMKII (T-CaMKII) were determined at different post-transfusion times by Western blot and immunostaining and were compared with controls.
  
  
  RESULTS
  P-CaMKII increased significantly (P<0.05) at 0, 0.5, and 2 hours. However, P-CaMKII at 5 to 24 hours and T-CaMKII at 0 to 24 hours post-transfusion did not change significantly in rats' spinal dorsal horn, hippocampus, or primary somatosensory (S1) cortex (n=6 per group). Similarly, immunostaining showed stronger P-CaMKII immunoreactants (P<0.05) and more P-CaMKII- positive cells (P<0.05) in the spinal dorsal horn, CA1 region of the hippocampus, and S1 cortex of rats 0.5 hours post-transfusion compared with the control group treated with 0.9% sodium chloride (n=3 per group).
  
  
  CONCLUSIONS
  These results suggest that a temporary rise in the P-CaMKII level in the central nervous system may correlate with remifentanil-induced pain sensitization in the postoperative period.
authors.affiliation: Department of Anesthesia, Capital Medical University-affiliated Beijing Friendship Hospital, Beijing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Shuren
authors.initials: S
authors.lastname: Li
authors.forename: Song
authors.initials: S
authors.lastname: Han
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Peng
authors.forename: Junfa
authors.initials: J
authors.lastname: Li
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001931:Brain Mapping / Q000379:methods; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D006930:Hyperalgesia / Q000188:drug therapy; D007262:Infusions, Intravenous; D008297:Male; D009020:Morphine / Q000494:pharmacology; D010766:Phosphorylation; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077208:Remifentanil; D013116:Spinal Cord / Q000187:drug effects; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D010880:Piperidines; D009020:Morphine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D000077208:Remifentanil
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