异丙酚对急性吗啡耐受小鼠痛觉过敏的影响

Effects of propofol on mice with acute morphine tolerance and hyperalgesia

目的观察异丙酚对急性吗啡耐受小鼠痛阈的影响。方法健康雌性小鼠56只，随机分成7组（n=8）：吗啡异丙酚组1（MP1）、吗啡异丙酚组2（MP2）、吗啡异丙酚组3（MP3）、大豆油对照组（SC）、生理盐水异丙酚组1（NSP1）、生理盐水异丙酚组2（NSP2）、生理盐水异丙酚组3（NSP3）。通过皮下注射吗啡建立急性吗啡耐受模型：MP1、MP2、MP3组和sc组小鼠皮下注射吗啡10mg／kg，2h一次，连续注射5次。建模成功后各组分别给予异丙酚10、30、50mg／kg和注射用大豆油10μl。NSP1、NSP2、NSP3组小鼠皮下注射生理盐水10mg／kg后腹腔给予异丙酚（NSPl组10mg／kg、NSP2组30mg／kg、NSP3组50mg／kg）。在各次皮下注射吗啡及腹腔注射异丙酚溶液后10、30、60、120min分别用热板法测量热缩足反应时间作为小鼠的热痛阈值。结果吗啡异丙酚组：与sc组相比，MP1组热痛阈值的差异无统计学意义（P〉0．05），MP2组和MP3组小鼠热痛阈值提高（P〈0．05）；MP2组、MP3组与MP1组相比热痛阈值提高（P〈0．05）；MP2组与MP3组小鼠热痛阈值的差异无统计学意义（P〉0．05）。生理盐水异丙酚组：注射生理盐水前后，小鼠热痛阈值的差异无统计学意义（P〉0．05）；腹腔注射异丙酚后，NP1、NP2、NP3组小鼠热痛阈值的差异无统计学意义（P〉0．05）。结论异丙酚对正常小鼠的热痛阈值无影响；异丙酚30mg／kg和50mg／kg能够使急性吗啡耐受和痛觉过敏的小鼠热痛阈值提高，拮抗吗啡镇痛耐受与痛觉过敏，但异丙酚10mg／kg拮抗作用不明显。

Objective To observe the effects of propofol on the pain threshold of mice with acute morphine toler- ance. Methods A total of 56 healthy female mice were randomly divided into seven groups （ n = 8） ： Groups morphine and propofol 1, 2 and 3 （MP1, MP2 and MP3）, Group soybean oil control （SC） and Groups normal saline and propofol 1, 2 and 3 （ NSP 1, 2 and 3）. A model of acute morphine tolerance was established through subcutaneous injection of morphine, where Groups MP 1,2 and 3 and Group SC were subcutaneously injected with 10 mg/kg morphine once every two hours for five consecutive times, followed by administration of 10 mg/kg propofol （ Group MP 1 ）, 30 mg/kg propofol （Group MP 2）, 50 mg/kg（ Group MP 3） as well as 10 μ1 soybean oil （Group SC）. In contrast, Groups NSP1, NSP2 and NSP3 were subcutaneously injected with 10 mg/kg normal saline followed by administration of 10 mg/kg propofol （Group NSP 1 ）, 30 mg/kg propofol （Group NSP 2）, and 50 mg/kg （Group NSP 3）. The paw withdrawal thermal la- tency was measured as the hot - pain thresholds of mice 10, 30, 60 and 120 rain after administration of propofol solution. Results Compared with Group SC, no significant difference was found in the hot - pain threshold of Group MP 1 （P 〉 0.05）, while increased hot - pain thresholds were observed in Groups MP 2 and 3 （P 〈 0.05）. Furthermore, compared with Group MP 1, both Groups MP 2 and 3 presented higher hot - pain thresholds （P 〈 0.05）. The hot - pain thresholds were no significantly different between Groups MP 2 and 3 （ P 〉 0.05）. Meanwhile, no statistical difference was found as to hot - pain threshold before and after injection of normal saline （ P 〉 0.05 ）. No statistical differences were found among Groups NSP1, NSP2 and NSP3 after subcutaneous injection of propofol （P 〉 0.05）. Conclusions Propofol produces no impact on the hot - pain threshold of normal mice. Administration of 30 mg/kg and 50 mg/kg propofol can enhance thehot - pain threshold of mice with acute morphine tolerance and hyperalgesia. However, lOmg/kg of propofol can not pro- duce obvious antagonist effects.