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.
