Gong Wen-Yi, Xu Bing, Liu Li, Li Shi-Tong
Department of Anesthesiology, Shanghai General Hospital of Nanjing Medical University, No.100, Haining Road, Hongkou District, Shanghai, 200080, People's Republic of China.
Department of Anesthesiology, Wusong Hospital, No.101, North Tongtai Road, Baoshan District, Shanghai, 200940, People's Republic of China.
Exp Brain Res. 2022 May;240(5):1435-1444. doi: 10.1007/s00221-022-06341-7. Epub 2022 Mar 25.
The relieving role of dezocine in pain after surgery was previously reported, while the potential mechanism was not completely clear. Therefore, the current research probed into the regulatory mechanism of dezocine in pain after surgery. A postoperative pain model was established by performing plantar incision surgery on the juvenile Sprague-Dawley rats. After the rats were treated with dezocine or SC79 (Akt1 activator), the paw withdrawal threshold and paw withdrawal latency of rats were detected to evaluate the mechanical allodynia and thermal hyperalgesia. After the plantar tissue, dorsal root ganglions, and spinal cord of rats were collected, the expressions of Akt1, p-Akt1, GSK-3β, and p-GSK-3β in the tissues were determined by western blot to evaluate the activation state of the Akt1/GSK-3β pathway. After surgery, the paw withdrawal threshold and paw withdrawal latency of rats were lessened, whereas the ratios of p-Akt1/Akt1 and p-GSK-3β/GSK-3β were augmented in rat plantar tissue, dorsal root ganglions, and spinal cord. After treatment with dezocine alone, the paw withdrawal threshold and paw withdrawal latency of postoperative rats were elevated, but ratios of p-Akt1/Akt1 and p-GSK-3β/GSK-3β were reduced. After co-treatment with dezocine and SC79, SC79 reversed the effects of dezocine on elevating the paw withdrawal threshold and paw withdrawal latency, and reducing the ratios of p-Akt1/Akt1 and p-GSK-3β/GSK-3β in postoperative rats. Dezocine ameliorated the postoperative hyperalgesia in rats via repressing the hyper-action of Akt1/GSK-3β pathway.
先前有报道称地佐辛在术后疼痛中具有缓解作用，但其潜在机制尚不完全清楚。因此，当前研究探讨了地佐辛在术后疼痛中的调节机制。通过对幼年Sprague-Dawley大鼠进行足底切口手术建立术后疼痛模型。在用 地佐辛或SC79（Akt1激活剂）处理大鼠后，检测大鼠的爪部撤离阈值和爪部撤离潜伏期，以评估机械性异常性疼痛和热痛觉过敏。收集大鼠的足底组织、背根神经节和脊髓后，通过蛋白质印迹法测定组织中Akt1、p-Akt1、GSK-3β和p-GSK-3β的表达，以评估Akt1/GSK-3β信号通路的激活状态。术后，大鼠的爪部撤离阈值和爪部撤离潜伏期降低，而大鼠足底组织、背根神经节和脊髓中p-Akt1/Akt1和p-GSK-3β/GSK-3β的比值升高。单独用地佐辛治疗后，术后大鼠的爪部撤离阈值和爪部撤离潜伏期升高，但p-Akt1/Akt1和p-GSK-3β/GSK-3β的比值降低。用地佐辛和SC79联合治疗后，SC79逆转了地佐辛对术后大鼠提高爪部撤离阈值和爪部撤离潜伏期以及降低p-Akt1/Akt1和p-GSK-3β/GSK-3β比值的作用。地佐辛通过抑制Akt1/GSK- 3β信号通路的过度激活来改善大鼠术后痛觉过敏。
