焦虑样情绪增强小鼠痛觉敏感性

EXACERBATION OF PAIN SENSATION IN ANXIOGENIC MICE

目的:建立焦虑小鼠模型,研究焦虑样情绪反应对小鼠基础痛阈及术后疼痛转归的影响,也为后续研究深入探讨情绪与痛觉相关的分子生物学机制提供动物模型基础。方法:1 20只雄性C57BL/6J小鼠,随机分为正常合笼饲养组(Social Group)和焦虑造模组(Isolation Group)2组,每组10只。焦虑造模后对比两组小鼠焦虑样情绪反应差异以及基础痛阈值的差异。2 32只雄性C57BL/6J小鼠,随机分为4组:正常假手术(SG Sham)、正常切口痛组(SG Incision)、焦虑假手术组(IG Sham)、焦虑切口痛组(IG Incision),检测各组小鼠术前(d0)以及术后3 h,1 d,3 d,5 d,8 d,10 d和16 d的von Frey机械性触痛觉敏感性的改变。结果:1经8周的焦虑造模后,模型组小鼠呈现明显的焦虑样行为,表现为体重降低,活动性增强以及探索行为的抑制;2焦虑模型组小鼠相比于正常组小鼠,机械性痛阈(17.9±5.52 cm vs 32.6±8.37 cm)及热甩尾阈值(1.10±0.55 s vs 3.38±1.24 s)均显著降低;3焦虑状态可加重小鼠足底切口术后的急性期触痛觉敏感性,并延长触痛敏的恢复时间。具体表现为在足底切口术后3 h,1 d,3 d,5 d的时间点,IG Incision组小鼠的触痛敏程度均强于同一时间点的SG Incision组小鼠,而SG Incision组小鼠在术后5天的触诱发痛阈值(1.80±0.31 g)与SG Sham组小鼠(2.00±0.00 g)已无显著差异(P>0.05),但IG Incision组在术后5天时痛阈(1.07±0.30 g)仍低于IG Sham组(1.73±0.43 g,P<0.05),术后8天,10天以及16天虽与IG Sham组无显著性差异(P>0.05),但仍然存在降低趋势。结论:1焦虑样情绪可降低小鼠机械性痛阈值及热痛阈值,并可增强小鼠切口术后触痛觉敏感性,延长术后触痛敏的恢复时间;2本研究中所应用的动物模型可作为情绪应激引起的痛觉增敏模型,为后续研究深入探讨情绪与痛觉相关的分子生物学机制提供动物模型基础。

Objective： To evaluate the relationship between anxiogenic emotion and pain sensation by establishing the anxiogenic mice model. Method： Firstly, we tried to explore whether anxiety mood may influence basal pain sensation. C57BL/6J mice of 4 weeks old were randomly divided into two groups （n = 10 per group）： Social Group （SG） and Isolation Group （IG）, the anxiety-like behavior in mice were induced by isolation combined with empty water bottle stress, the total duration was 8 weeks. Mechanical pain threshold and thermal pain threshold were measured after 8 weeks. Secondly, we established the hind paw incision model, which is considered to be representative of post surgical pain in human, to explore whether this kind of negative mood may influence the recovering of post surgical pain. C57BL/6J mice were randomly divided into 4 groups ：SG Sham, SG Incision, IG Sham and IG Incision （n = 8 per group）. Post operational allodynia was measured by yon Frey test at 3 h, 1 d, 3 d, 5 d, 8 d, 10 d and 16d. Results： （1） Compared with the control SG group, mice in IG group exhibited obvious anxiety-like behavior, including slow growth inbody weight, hyperactivity and reduced exploration behavior; （2） Basal pain threshold, both mechanical pain threshold （ 17.9±5.52 cm vs 32.6±8.37 cm ） and tail flick latency （1.10±0.55 s vs 3.38± 1.24s ） were significantly lower in the anxiety group than in the control group; （3） Postoperative hyperalgesia was enhanced in anxiogenic mice and the recovery time was lengthened. Condusion： （1） Basal pain sensation was exacerbated in anxiogenic mice and postoperative hyperalgesia enhanced together with a prolonged recovery time; （2） Our animal model may serve as stress-induced hyperalgesia model for further research.