吗啡联合不同剂量丁丙诺啡对大鼠骨癌痛疼痛行为学实验的影响

Effect of morphine combined with buprenorphine in different doses on pain behavior of bone cancer in rats

目的研究吗啡联合不同剂量的丁丙诺啡对大鼠骨癌痛疼痛行为学实验的影响。方法取60只健康成年雌性Wistar大鼠,通过Walker 256细胞制备骨癌痛动物模型,将实验大鼠随机分为假手术组(皮下注射0.9%氯化钠溶液1 mL)、吗啡组(皮下注射吗啡10 mg/kg)、联合1组(皮下注射吗啡10 mg/kg联合丁丙诺啡20μg/kg),联合2组(皮下注射吗啡10 mg/kg联合丁丙诺啡40μg/kg)、联合3组(皮下注射吗啡10 mg/kg联合丁丙诺啡60μg/kg),每组各12只,均连续给药1周。造模2周后,每日均进行热痛觉敏感度、机械性痛觉敏感度及甩尾实验,实验时间为1周。结果吗啡组给药第1~4 d时热痛阈值明显高于假手术组(P<0.05),第5~7 d时热痛阈值与假手术组比较差异无统计学意义(P>0.05)。联合1组、联合3组给药第1~3 d时热痛阈值明显高于假手术组(P<0.05),联合1组第1~3 d、联合3组第2~3 d时热痛阈值均低于吗啡组(均P<0.05)。第4~7 d时联合1组、联合3组热痛阈值与假手术组比较差异均无统计学意义(均P>0.05)。吗啡组给药第5 d时出现热痛阈值明显下降,而联合2组在第6 d时出现热痛阈值下降,与假手术组比较差异均无统计学意义(均P>0.05)。随着给药时间的延长,吗啡组与各联合组机械阈值和抗伤害痛阈值均明显下降(P<0.05)。假手术组不同时间机械阈值和抗伤害痛阈值比较差异均无统计学意义(均P>0.05);吗啡组与各联合组不同时间的机械痛阈值和抗伤害痛阈值均明显高于假手术组(均P<0.05);联合1组、联合2组、联合3组给药1周机械痛阈值、抗伤害痛阈值与吗啡组比较差异均无统计学意义(均P>0.05)。结论吗啡联合不同剂量的丁丙诺啡对骨癌痛大鼠的镇痛效果相当,但吗啡10 mg/kg联合丁丙诺啡40μg/kg应用时可延迟吗啡的耐受发生。

Objective To study the effect of morphine combined with buprenorphine in different doses on pain behavior of bone cancer in rats.Methods 60 healthy adult female Wistar rats were randomly divided into sham operated group(1 mL of 0.9%sodium chloride solution subcutaneously),morphine group(10 mg/kg of morphine subcutaneously),combined group 1(10 mg/kg of morphine subcutaneously combined with 20μg/kg of buprenorphine),combined group 2(10 mg/kg of morphine subcutaneously combined with 40μg/kg of buprenorphine),combined group 3(10 mg/kg of morphine subcutaneously combined with 60μg/kg buprenorphine),12 rats in each group.All of rats were treated for one week.After 2 weeks of modeling,the experiments of thermal sensitivity,mechanical sensitivity and tail flick were carried out every day for 1 week.Results The thermal pain threshold of morphine group was significantly higher than that of sham operation group(P<0.05)on day 1-4,and there was no significant difference between the two groups on day 5-7(P>0.05).The thermal pain threshold of combination group 1 and combination group 3 was significantly higher than that of sham operation group on day 1-3,and that of combination group 1 and combination group 3 was lower than that of morphine group on day 2-3(P<0.05)and combination group 4-7(P<0.05).Compared with the sham operation group,there was no significant difference in the thermal pain threshold between the combined group and the sham operation group(P>0.05).With the prolongation of administration time,the mechanical threshold and anti injury threshold of morphine group and each combination group decreased significantly(P<0.05).The mechanical threshold and anti injury threshold of sham operation group at different times had no significant difference(P>0.05).The mechanical threshold and anti injury threshold of morphine group and each combination group at different times were significantly higher than those of sham operation group(P<0.05).There was no significant difference in mechanical pain threshold and anti injury pain threshold between the combined group 1,2 and 3 and the morphine group(P>0.05).Conclusion Morphine combined with buprenorphine of different doses has the same analgesic effect on bone cancer pain rats,and can delay the occurrence of morphine tolerance.