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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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柱上的过程，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，该测试不能解释疼痛的情感动机或认知成分。我们引入了双重回避位置偏好范例，这是一种在自由移动的大鼠中进行的综合测试程序，该程序依赖于避免激活热坡道的暗室与逃向令人厌恶的明亮室之间的冲突。我们能够区分第一个伤害性阈值和最终逃离暗室的温度，从而传达有关动物适应性行为的信息。一小时后重复测量，以评估再次暴露后的适应性学习反应。在幼稚动物中，在再次暴露后，在测试范式的所有阶段中在暗室中花费的时间都显着减少，导致在洪水达到伤害性值之前最终逃脱。这种适应性行为因抗焦虑治疗而减弱。在足底内注射完全弗氏佐剂后表现出痛觉过敏的动物中，逃避阈值显着高于对照动物，暗示对有害刺激的适应不良的情感动机反应。然而，在袖带动物中，我们未能发现任何热伤害性超敏反应，但动物在再次暴露后表现出对冷模拟的强烈适应性反应。总体而言，所提出的范例允许综合皮质反应导致主动回避行为，同时完全符合动物实验的道德标准。