SBIR-STTR Award

Reflexes are not always good predictors of clinical pain. There is a need for methods for measuring pain responses of animals at the conscious level. The Aim of this Project is to develop an apparatus for testing operant nociceptive responses "conscious pain sensitivity" exhibited by rodents. This apparatus can be used to evaluate the effect of a disease state, drug, surgical procedure or other intervention, on pain sensitivity. The apparatus will be designed to measure a conscious escape response to painful hot and cold stimuli and an aversive non-painful bright light stimulus. The apparatus will include two chambers connected by a portal which will allow the test animal to pass between the two chambers even if the animal is tethered to infusion cannulas, cables, or other diagnostic or delivery devices. The two chambers will be able to independently produce painful conditions by using floors that can be rapidly heated or rapidly cooled using Peltier devices. Therefore the floor of each chamber can be at a comfortable temperature, or painfully hot or painfully cold (two way shuttle test). The ability to change floor temperature rapidly allows for repeated trials with minimal avoidance learning. Each chamber will be able to produce an aversive, non-painful condition, using bright light. The bright light in each chamber can be independently turned on or off (two way control). The two chambers will be equipped with photo-electronic sensing devices to automatically record the movements of the animal between the two chambers. Computer software will control the experimental conditions and record escape latency measurements, place preference data, and baseline control data. The apparatus can be outfitted with a tether to the rodent to allow the application of electrical or chemical stimuli or to take biological samples. Stimulation through the tether can be in lieu of, or concurrent with, the thermal floor stimuli. Thus the apparatus will be flexible and applicable to a variety of pain sensitivity studies

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.

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