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Repeated exposure of naïve and peripheral nerve-injured mice to a snake as an experimental model of post-traumatic stress disorder and its co-morbidity with neuropathic pain.

将初始和外周神经损伤小鼠重复暴露于蛇作为创伤后应激障碍的实验模型及其与神经病理性疼痛的共病。

  • 影响因子:3.15
  • DOI:10.1016/j.brainres.2020.146907
  • 作者列表:"Mendes-Gomes J","Paschoalin-Maurin T","Donaldson LF","Lumb BM","Blanchard DC","Coimbra NC
  • 发表时间:2020-10-01
Abstract

:Confrontation of rodents by natural predators provides a number of advantages as a model for traumatic or stressful experience. Using this approach, one of the aims of this study was to investigate a model for the study of post-traumatic stress disorder (PTSD)-related behaviour in mice. Moreover, because PTSD can facilitate the establishment of chronic pain (CP), and in the same way, patients with CP have an increased tendency to develop PTSD when exposed to a traumatic event, our second aim was to analyse whether this comorbidity can be verified in the new paradigm. C57BL/6 male mice underwent chronic constriction injury of the sciatic nerve (CCI), a model of neuropathic CP, or not (sham groups) and were submitted to different threatening situations. Threatened mice exhibited enhanced defensive behaviours, as well as significantly enhanced risk assessment and escape behaviours during context reexposure. Previous snake exposure reduced open-arm time in the elevated plus-maze test, suggesting an increase in anxiety levels. Sham mice showed fear-induced antinociception immediately after a second exposure to the snake, but 1 week later, they exhibited allodynia, suggesting that multiple exposures to the snake led to increased nociceptive responses. Moreover, after reexposure to the aversive environment, allodynia was maintained. CCI alone produced intense allodynia, which was unaltered by exposure to either the snake stimuli or reexposure to the experimental context. Together, these results specifically parallel the behavioural symptoms of PTSD, suggesting that the snake/exuvia/reexposure procedure may constitute a useful animal model to study PTSD.

摘要

: 天敌对啮齿动物的对抗作为创伤性或应激性经验的模型提供了许多优势。使用这种方法,本研究的目的之一是研究小鼠创伤后应激障碍 (PTSD) 相关行为的模型。此外,由于 PTSD 可以促进慢性疼痛 (CP) 的建立,并且以同样的方式,CP 患者在暴露于创伤性事件时发展 PTSD 的趋势增加,我们的第二个目的是分析这种共病是否可以在新的范式中得到验证。C57BL/6 雄性小鼠接受坐骨神经慢性缩窄性损伤 (CCI) (神经病理性 CP 模型),或不接受 (假手术组),并接受不同的威胁情况。受威胁的小鼠表现出增强的防御行为,以及在环境再暴露期间显著增强的风险评估和逃避行为。既往蛇暴露减少了高架加迷宫测试中的张开时间,提示焦虑水平增加。假小鼠在第二次暴露于蛇后立即表现出恐惧诱导的抗伤害感受,但 1 周后,它们表现出异常性疼痛,表明多次暴露于蛇导致伤害性反应增加。此外,在再次暴露于厌恶的环境后,异常性疼痛得以维持。CCI 单独产生强烈的异常性疼痛,暴露于蛇刺激或再暴露于实验环境中没有改变。总之,这些结果与 PTSD 的行为症状特别平行,表明 snake/exuvia/再暴露程序可能构成研究 PTSD 的有用动物模型。

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