丁丙诺啡与吗啡联合用于大鼠骨癌痛治疗的疼痛行为学观察

目的 观察不同剂量的丁丙诺啡与吗啡联合应用于大鼠骨癌痛的疼痛行为学变化，为临床合理应用阿片类药物治疗癌痛提供参考。方法 选择成年雌性Wistar大鼠进行实验，应用Walker256细胞建立骨癌痛模型，将骨癌痛大鼠分为5组，每组8只，分别于每日7:00 am和19:00 pm进行皮下注射，连续7日。吗啡组（M组）：吗啡10 mg/kg；吗啡+丁丙诺啡1组（MB1组）：吗啡10 mg/kg+丁丙诺啡20μg/kg；吗啡+丁丙诺啡2组（MB2组）：吗啡10 mg/kg+丁丙诺啡40 μg/kg；吗啡+丁丙诺啡3组（MB3组）：吗啡10 mg/kg+丁丙诺啡60 μg/kg；假手术组（Sham组）：皮下注射0.9%氯化钠溶液1 ml。全部大鼠于建模第15天开始，每日给药前30 min、给药后30 min进行疼痛行为学测定，包括甩尾实验、机械性痛觉敏感度测定、热痛觉敏感度测定。结果 给药7天内，机械痛阈和甩尾实验测定抗伤害痛阈结果显示，各MB组与M组给药后痛阈差异均无统计学意义；热痛阈结果显示：MB2组出现明显的热痛阈下降较M组晚（第6天vs.第5天）。结论 骨癌痛大鼠癌痛治疗时，丁丙诺啡与吗啡联合应用镇痛作用相似且可延缓吗啡的耐受发生。

Pain Behavior Observation of Buprenorphine Combined with Morphine on Bone Cancer Pain in Rat Model

Objective To investigate the therapeutic effects of different doses of buprenorphine combined with morphine on bone cancer pain in a rat model. Methods Female adult Wistar rats were selected for this experiment. After Walker256 rat breast cancer cells were subcutaneously injected into the left tibia of the rats to induce bone cancer pain, the model rats were divided into 5 groups (n=8 for each): M (mophine 10 mg/kg), MB1(morphine 10 mg/kg+ buprenorphine 20 μg/kg), MB2 (morphine 10 mg/kg+ buprenorphine 40 μg/kg), MB3 (morphine 10 mg/kg+ buprenorphine 60 μg/kg) and Sham (isotonic saline 1 ml). Morphine and/or buprenorphine were subcutaneously given twice a day (at 7:00 am and 7:00 pm, respectively) for 7 consecutive days. From day 15, all rats underwent behavioral pain tests including tail flick test, mechanical pain sensitivity test and thermal pain sensitivity test 30 min before and after drug adminstration at 7:30 am. Results Antinociceptive and mechanical pain threshold showed no significant difference between MB groups and M group. The presence of significant decrease in thermal pain threshold in MB2 group was later than that in M group (6th day vs. 5th day). Conclusion In the treatment for cancer pain in rats, the combination of morphine and buprenorphine has similar antinociceptive effect to morphine, moreover, it may delay morphine tolerance.