Dezocine Attenuates The Remifentanil-induced Postoperative Hyperalgesia By Inhibiting The Phosphorylation Of CaMKⅡα

Object:To investigate whether dezocine could alleviate remifentanil-induced postoperative hyperalgesia（RIPH）by inhibiting the phosphorylation of Ca²⁺/calmodulin-dependent protein kinaseⅡα（CaMKⅡα）,and to investigate the relationship between CaMKⅡαand postoperative hyperalgesia in peripheral and central pain transmission pathways.Methods:Using a mouse model of incisional postoperative pain,63 ICR male mice（30-35g）were randomly divided into 7 groups:NS group（saline group）;I group（plantar incision surgery group）;R group（remifentanil group）;R+DeL group（remifentanil+low dosage of dezocine group）;R+DeM group（remifentanil+middle dosage of dezocine group）;R+DeH group（remifentanil+high dosage of dezocine group）;R+K group（remifentanil+ketamine group）.Paw withdrawal thermal latency（PWTL）and paw withdrawal mechanical threshold（PWMT）were used to assess thermal hyperalgesia and mechanical allodynia at 1d before and 0.5h、2h、5h、24h after surgery.Western blot and immunohistochemistry analysis were used to assess the expression of phosphorylated CaMKⅡα（p-CaMKⅡα）in somatosensory cortex,hippocampus and spinal cord（L4-L6）at 2h after surgery.Result:Compared with NS group,mice in I group showed decrease in PWTL and PWMT at 0.5h、2h after surgery.Compared with I group,mice in R group showed significant decrease in PWTL and PWMT at 0.5h、2h、5h after surgery.Compared with R group,mice in R+K group showed increase in PWTL and PWMT at 0.5h、2h、5h after surgery.Compared with R group,mice in R+DeL group,R+DeM group and R+DeH group showed dose-dependent increase in in PWTL and PWMT at0.5h、2h、5h after surgery.Correlating with behavioral effects,western blot analysis and immunohistochemistry analysis suggested that compared with I group,mice in R group showed significant increase in p-CaMKⅡαexpression in somatosensory cortex,hippocampus and spinal cord.Compared with R group,mice in R+K group showed decrease in p-CaMKⅡαexpression in somatosensory cortex,hippocampus and spinal cord.Compared with R group,mice in R+DeM group and R+DeH group showed significant decreased in p-CaMKⅡαexpression in somatosensory cortex,hippocampus and spinal cord.Conclusion:Sustained administration of remifentanil during anesthesia enhanced post-incisional pain and induced postoperative hyperalgesia.Dezocine could attenuate remifentanil-induced postoperative hyperalgesia（RIPH）by suppressing phosphorylation of CaMKⅡαin somatosensory cortex,hippocampus and spinal cord.