Apparatus for Testing Pain Sensitivity in Rodents

项目描述（由申请人提供）：该项目的目标是建立和测试一种研究工具的原型，用于研究疼痛机制和筛选潜在的新型止痛药的效果。该系统由硬件和软件组成，旨在测量啮齿动物（大鼠和小鼠）的热痛敏感性，该系统基于对爪子的热刺激（热或冷）诱导的习得性（皮质介导的）逃避行为。该设备的特点是一个测试室，有两个温度控制的地板区域（一个通常处于令人痛苦的温度，另一个热中性）。动物从疼痛区域逃到中性区域的延迟是被测量的反应。在每次逃离后，动物会通过打开明亮的光来激励自己回到刺激表面（明亮的光对啮齿动物来说是厌恶的，它们会逃离它）。这允许以自动化的方式进行多次逃跑试验，而不需要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跑反应的影响。与现有的疼痛测试相比，一个主要的优势是，测量的逃避反应可以由中等刺激强度引起，并作为人类临床疼痛的模型，依赖于伤害性信号的时间整合。新方法为科学家和药物开发人员提供了一种替代方法，该方法考虑到比传统的基于反射的啮齿动物疼痛测试更大程度上更高水平疼痛处理的贡献。因此，该方法扩大了可能在动物身上进行的测试范围，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，因为动物不受约束，在测试过程中不与人类接触，完全控制刺激的开始和结束。该项目将完善新的热手术疼痛敏感性测试的硬件和软件，使其成为一种可靠、灵活和用户友好的工具，可供研究人员在商业上销售。

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.