Although the behavioral response to pain is complex and involves supraspinal processes, assessment of pain symptoms in animal models still mainly relies on reflex-based nociceptive tests, which do not account for the affective-motivational nor cognitive components of pain. We introduce a double avoidance place preference paradigm, an integrated testing procedure in freely moving rats that relies on the conflict between the avoidance of a dark compartment in which a thermal ramp is activated, and the escape towards an aversive brightly lit compartment. We were able to differentiate the first nociceptive threshold from the temperature of definitive escape from the dark compartment, conveying information on the adaptive behavior of animals. Measures were repeated after an hour to evaluate the adaptive learning response upon reexposure. In naive animals, there was a significant decrease in the time spent in the dark compartment at all stages of the testing paradigm upon reexposure, leading to a final escape before the flood had reached nociceptive values. This adaptive behavior was blunted by anxiolytic treatment. In animals exhibiting hyperalgesia following intraplantar complete Freund adjuvant injection, escape thresholds were significantly higher than that of control animals, hinting at a maladaptive affective-motivational response to noxious stimulation. However, in cuff animals, we failed to reveal any hot nociceptive hypersensitivity, but animals exhibited a strong adaptive response to cold simulation upon reexposure. Overall, the proposed paradigm allows for an integrated cortical response leading to a proactive avoidance behavior, while fully complying with ethical standards in animal experimentation.

中文翻译：

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在 Scylla 和 Charybdis 之间：使用双重回避位置偏好范式评估大鼠疼痛行为的多维方面。


尽管对疼痛的行为反应很复杂并且涉及脊髓上过程，但动物模型中疼痛症状的评估仍然主要依赖于基于反射的伤害性测试，这些测试没有考虑疼痛的情感动机或认知成分。我们引入了一种双重回避位置偏好范式，这是一种在自由移动的大鼠中进行的综合测试程序，它依赖于避免激活热斜坡的黑暗隔间与逃脱到令人厌恶的明亮隔间之间的冲突。我们能够区分第一个伤害性阈值和最终逃离黑暗隔间的温度，传达有关动物适应行为的信息。一小时后重复测量以评估再次暴露时的适应性学习反应。在幼稚的动物中，在再次暴露后，在测试范式的所有阶段在黑暗隔间中花费的时间都显着减少，导致在洪水达到伤害感受值之前最后一次逃脱。这种适应性行为被抗焦虑治疗减弱。在足底内完全弗氏佐剂注射后表现出痛觉过敏的动物中，逃逸阈值显着高于对照动物，暗示对有害刺激的适应不良情感动机反应。然而，在袖带动物中，我们未能揭示任何热伤害性超敏反应，但动物在再次暴露时对冷模拟表现出强烈的适应性反应。总体而言，所提出的范式允许综合皮层反应导致主动回避行为，同时完全符合动物实验中的道德标准。