Apparatus for Testing Pain Sensitivity in Rodents

描述（由申请人提供）：该项目的目标是构建和测试研究工具的原型，用于研究疼痛机制和筛选潜在的新型止痛药物的效果。该系统由硬件和软件组成，旨在根据对爪子的热刺激（热或冷）诱导的习得（皮质介导）逃避行为来测量啮齿类动物（大鼠和小鼠）的热痛敏感性。该设备的特点是测试室有两个温度受控的地板区域（一个通常处于令人痛苦的温度，另一个处于热中性）。动物从疼痛区域逃到中性区域的延迟时间就是测量到的反应。每次逃脱后，动物都会通过打开亮光而返回刺激表面（啮齿动物厌恶亮光，它们会逃跑）。这允许以自动方式进行多次逃脱试验，而无需在试验之间处理动物。该系统包括一个控制测试，用于测量与疼痛无关的逃避反应的影响。与现有疼痛测试相比的一个主要优点是，测量的逃避反应可以通过中等刺激强度引发，并作为依赖于伤害性信号的时间整合的人类临床疼痛模型。新方法为科学家和药物开发人员提供了一种方法替代方案，与传统的基于反射的啮齿动物疼痛测试相比，该方法在更大程度上考虑了更高水平的疼痛处理的贡献。因此，该方法扩展了动物可能进行的测试范围，并减少了对潜在风险和更昂贵的人体实验的需求。新的测试比传统的基于反射的测试更人性化，压力更小，因为动物在测试过程中不受约束，不与人类接触，并且完全控制刺激的开始和结束。该项目将完善新型热操作疼痛敏感性测试的硬件和软件，使其成为研究人员可靠、灵活且用户友好的工具，并具有商业价值。

DESCRIPTION (provided by applicant): The goal of the project is to build and test prototypes for a research tool for investigating pain mechanisms and for screening prospective new pain-relieving drugs for their effect. The system consists of hardware and software designed to measure thermal pain sensitivity of rodents (rats and mice) based upon learned (cortically mediated) escape behaviors that are induced by thermal stimuli (hot or cold) to the paws. The apparatus features a testing chamber with two temperature-controlled floor areas (one typically at a painful temperature, the other thermally neutral). The delay with which the animal escapes from the painful to the neutral area is the measured response. After each escape the animal is motivated to return to the stimulus surface by turning on a bright light (bright light is aversive to rodents and they will escape it). This allows conducting multiple escape trials in an automated manner without the need for handling the animal between trials. The system includes a control test for measuring effects on the escape response that are not pain-related. A major advantage over existing pain tests is that the measured escape responses can be elicited by moderate stimulus intensities and serve as a model of human clinical pain that depends on temporal integration of nociceptive signals. The new method provides the scientist and drug developer with a methodological alternative that takes into account the contribution of higher level pain processing to a much larger degree than traditional reflex-based rodent pain tests. The method therefore extends the range of tests that are possible with animals and reduces the need for potentially risky and more expensive human experiments. The new test is more humane and less stressful than traditional reflex-based tests because the animals are not restrained, not in contact with humans during the test and in full control over stimulus onset and end. This project will refine the hardware and software of the new thermal operant pain sensitivity test to the point that it is a reliable, flexible and user-friendly tool for investigators that is commercially marketable.