title: CaMKII Phosphorylation in Primary Somatosensory Cortical Neurons is Involved in the Inhibition of Remifentanil-induced Hyperalgesia by Lidocaine in Male Sprague-Dawley Rats.
abstract: BACKGROUND
  Previous clinical studies have shown that lidocaine can alleviate severe postoperative pain after remifentanil-based anesthesia. Experimental studies have also demonstrated that lidocaine can inhibit remifentanil-induced hyperalgesia, yet the mechanism remains unknown. The present study explored the role of the primary somatosensory (S1) cortex in remifentanil-induced hyperalgesia as well as its inhibition by lidocaine through evaluation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) phosphorylation and protein expression levels in S1 cortical neurons.
  
  
  METHODS
  Male Sprague-Dawley rats were randomly allocated to the following 3 groups: remifentanil only (R), lidocaine only (L), and remifentanil+lidocaine (RL). Experimentally naive animals were used as controls for immunoblotting and immunofluorescence evaluations. Via intravenous tail vein administration (24 G catheter), the animals received remifentanil at 2.4 μg/kg/min, lidocaine at 200 μg/kg/min, and remifentanil at 2.4 μg/kg/min plus lidocaine at 200 μg/kg/min for 2 hours. Paw withdrawal threshold (PWT) values for both mechanical and thermal hyperalgesia, along with immunoblotting and immunofluorescence, were used to measure remifentanil-induced hyperalgesia and changes in CaMKII phosphorylation (P-CaMKII) and total protein expression (T-CaMKII).
  
  
  RESULTS
  There was a significant decrease in the PWT for mechanical stimulation at 0.5 and 2 hours after discontinuing infusion in groups R and RL (P<0.05, n=10 per group). However, there were no differences in thermal PWT in any group at any time period when compared with that of baseline. There was also a significant increase of P-CaMKII (not T-CaMKII) in S1 cortical neurons of group R (not L and RL groups) at 0 to 2 hours after discontinuing infusion when compared with that of the corresponding control group (P<0.05, n=6 per group) as determined by immunoblotting and immunofluorescence microscopy.
  
  
  CONCLUSIONS
  These results suggested that the phosphorylation of CaMKII in S1 cortical neurons increases significantly during the process of remifentanil-induced hyperalgesia. The increase of CaMKII phosphorylation could be inhibited by systemic application of lidocaine. This inhibition may play a role in the antihyperalgesia effects of lidocaine.
authors: *Department of Anesthesiology, Capital Medical University affiliated Beijing Tiantan Hospital†Department of Anesthesiology, Capital Medical University School of Rehabilitation Medicine‡Department of Neurobiology, Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, P.R. China.
authors: Weihua
authors: W
authors: Cui
authors: Shanshan
authors: S
authors: Wang
authors: Ruquan
authors: R
authors: Han
authors: Qiang
authors: Q
authors: Wang
authors: Junfa
authors: J
authors: Li
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D009474:Neurons; D010766:Phosphorylation / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077208:Remifentanil; D013003:Somatosensory Cortex / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; D000779:Anesthetics, Local; D010880:Piperidines; D008012:Lidocaine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D000077208:Remifentanil