Intrathecal injection of KN93 attenuates paradoxical remifentanil-induced postoperative hyperalgesia by inhibiting spinal CaMKII phosphorylation in rats.
OBJECTIVE
Remifentanil is a short-acting and highly selective mu opiate agonist that is used in many clinical surgical situations for intraoperative pain relief. Under certain conditions, remifentanil can produce "paradoxical" hyperalgesia. This study aims to investigate mechanisms of actions mediating this "paradoxical" effect.


METHODS
Sprague-Dawley rats were divided into 6 groups including control and treatment groups. The paw withdrawal mechanical threshold and the paw withdrawal thermal latency of the rats were tested. The changes of rat behaviors were measured at 24h before intrathecal injection and at 2h, 6h, 24h, and 48h after operation. According to the changes in behavioral indicators of pain, the specimens of all groups were collected at 2h, 6h, 24h, and 48h after the operation. The level of calcium/calmodulin-dependent protein kinase II (CaMKII) phosphorylation in the spinal dorsal horn was analyzed by Western blotting.


RESULTS
Intraoperative infusion of remifentanil induced postoperative hyperalgesia in the rats. Intrathecal KN93 injection increased nociceptive thresholds of paw withdrawal mechanical threshold and paw withdrawal thermal latency in a dose-dependent manner. Western blotting results showed that CaMKII phosphorylation in the spinal dorsal horn was increased significantly by remifentanil. Inhibition of CaMKII phosphorylation relieved the hyperalgesia pain state.


CONCLUSIONS
Intrathecal injection of KN93 attenuates postoperative hyperalgesia induced by intraoperative infusion of remifentanil in rats through inhibiting spinal CaMKII phosphorylation.
Department of Anesthesiology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, PR China.
Ming
M
Jiang
Department of Anesthesiology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, PR China.
Wei
W
Zhang
Department of Anesthesiology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, PR China.
Chongxue
C
Cheng
Department of Anesthesiology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, PR China. Electronic address: 13611586781@163.com.
Zhengliang
Z
Ma
Department of Anesthesiology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, PR China. Electronic address: njgxp1970@163.com.
Xiaoping
X
Gu
D000818:Animals; D001596:Benzylamines / Q000008:administration & dosage* / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control*; D007278:Injections, Spinal; D008297:Male; D010149:Postoperative Pain / Q000139:chemically induced*; D010880:Piperidines / Q000009:adverse effects*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077208:Remifentanil; D013116:Spinal Cord / Q000196:embryology*; D013449:Sulfonamides / Q000008:administration & dosage* / Q000494:pharmacology; D000096926:Benzenesulfonamides
D001596:Benzylamines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D000077208:Remifentanil; D013449:Sulfonamides; C072105:KN 93; D000096926:Benzenesulfonamides
Incisional surgery; KN93; Pain behavior; Phosphorylation; Remifentanil; Spinal dorsal horn