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啮齿类动物暴露于各种环境和实验等应激刺激条件下,产生许多行为和生理性应激反应[1-2]。应激刺激可致啮齿类动物痛阈升高,痛觉敏感性降低而诱发镇痛,即应激镇痛。测定痛阈的方法有压尾法、甩尾法、热板法和压脚法等[1]。根据应激刺激的特点(如应激源,持续时间,强度和时间模式),镇痛可能由内源性阿片系统或其他非阿片的激素和神经生化机制调解[2-3]。
旋转刺激可诱发啮齿类动物发生晕动病症状,例如异食癖,条件性厌食症,自发活动减少和激素水平变化等[4-6]。肾上腺酮等激素水平的升高,提示某些前庭刺激,如旋转亦可诱发啮齿类动物应激镇痛反应,引起应激镇痛的旋转亦是诱发啮齿类动物晕动病的有效前庭刺激条件。可见,以角加速度为主的平面旋转刺激,可诱发小鼠晕动病和应激镇痛反应。因此,研究旋转诱发的晕动病与应激镇痛之间功能联系的机制非常有意义[7-8]。二者都是通过相同的前庭刺激引起的,反应程度都依赖于应激刺激强度、类型和持续时间等。而且,重复的旋转刺激易致小鼠对镇痛耐受和晕动病的习服。
本实验以热板潜伏期为指标,在以角加速度为主的水平旋转刺激下,观察了化学迷路切除对小鼠旋转诱发的应激镇痛和吗啡镇痛的影响。
Effects of chemical labyrinthectomy on stress analgesia induced by rotation in mice
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摘要:
目的 探讨前庭器官在旋转诱发的小鼠应激镇痛中的作用。 方法 雌性小鼠随机分为吗啡组和旋转组,每组小鼠腹腔注射纳洛酮或生理盐水15 min后,观察给予吗啡或旋转(转速250 r/min,时间1 min,每旋转15 s暂停5 s)刺激后的热板潜伏期。另取小鼠连续7 d皮下注射吗啡形成耐受后,观察吗啡耐受小鼠旋转后的热板潜伏期。最后,内耳注射对氨基苯胂酸损伤小鼠前庭器官,观察化学迷路切除小鼠旋转后的热板潜伏期。 结果 与生理盐水组比较,纳洛酮组小鼠旋转后热板潜伏期无明显变化(P>0.05),皮下注射吗啡后热板潜伏期显著下降(P<0.05)。吗啡耐受小鼠旋转后热板潜伏期与生理盐水组比较无明显变化(P>0.05)。内耳注射对氨基苯胂酸后,小鼠接触翻正反射恢复时间显著增加、游泳能力显著下降(P<0.05),且化学迷路切除小鼠旋转后热板潜伏期显著缩短(P<0.05)。 结论 化学迷路切除完全阻滞了旋转诱发的小鼠应激镇痛。前庭器官在旋转诱发的应激镇痛中起重要作用,且该应激镇痛可能由非阿片系统介导。 Abstract:Objective To investigate the role of vestibular organs on stress analgesia induced by rotation in mice. Methods Female mice were randomly divided into morphine group and rotation group. After 15 minutes of intraperitoneal injection of naloxone or normal saline, the hot plate latency of mice in each group was observed following morphine injection or rotation (250 r/min, 15 s on with 5 s off). After subcutaneous injecting morphine for 7 consecutive days, tolerance was formed and the hot plate latency in morphine-tolerant mice after rotation was observed. P-aminophenylarsonic acid was injected into the inner ear to damage the vestibular organs of the mice and the hot plate latency was observed in chemically labyrinthectomy mice. Results Compared with the normal saline group, the hot plate latency of mice in the naloxone group did not change significantly after rotation (P>0.05), and the hot plate latency decreased significantly after subcutaneous injection of morphine (P<0.05). The morphine-tolerant mice had no significant change in the hot plate latency after rotation compared with the normal saline group (P>0.05). After injection of p-aminophenylarsonic acid into the inner ear, the recovery time of the righting reflex in mice was significantly increased, and the swimming ability was significantly reduced (P<0.05), and the hot plate latency of mice with chemical labyrinthectomy was significantly shortened after rotation (P<0.05). Conclusion Chemical labyrinthectomy completely blocked the rotation-induced stress analgesia in mice. Vestibular organs play an important role in rotation-induced stress analgesia, and this stress analgesia may be mediated by a non-opioid system. -
Key words:
- rotation /
- morphine /
- stress-induced analgesia /
- vestibular organs
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