Operant Behavioral Instrument for Measuring Pain in Rodents

慢性疼痛仍然是社会的主要负担，严重影响数百万人，每年花费数十亿美元。尽管我们对疼痛的理解取得了重大进展，但很少有新的疗法成功地转化为临床护理。这种翻译的特别不足是由于缺乏可靠的、高通量的、可商购的啮齿动物体内测定，特别是小鼠体内测定。为了解决这一问题，我们提出了一种创新的，自动化的，操作性的行为方法来评估啮齿动物的疼痛，我们的长期目标是建立一个操作性的模型系统，将快速，系统，有效地评估疼痛。 中心假设是，操作性测定可以提供一个敏感的，可靠的，临床相关的方式来评估感觉和伤害性处理。一个具体的目标将进行调查：评价小鼠操作模型的热痛觉过敏和异常性疼痛相比，大鼠操作模型研究疼痛。我们将使用一种非常创新的、自动化的、高通量的方法来测试小鼠和大鼠的疼痛和镇痛。这包括使用奖励冲突策略来评估热疼痛。拟议研究的基本原理是，在大鼠和小鼠中使用这些操作性测定来评估疼痛将为未来研究疼痛疾病的机制提供更好的方法。这项研究探索了一种用于评估疼痛动物模型的创新方法，并通过提供一种快速可靠的啮齿动物疼痛测试系统来显着推进新治疗方法的开发。待开发的产品和工艺是一种自动化、用户友好、不依赖于灭菌器、高通量、体内疼痛和止痛剂测试系统。鉴于Stoelting公司在开发产品方面的专业知识以及Neubert博士和Caudle博士的疼痛研究经验，我们特别适合完成这项工作。这一系列研究意义重大，因为它探索了一种新的、高通量的方法来评估镇痛剂给药后的疼痛和疼痛缓解。如果这一系列研究取得成功，其结果将对筛选和评估新的止痛疗法的方式产生重大影响，最终大大缩短新药临床上市的时间。

DESCRIPTION (provided by applicant): Chronic pain remains a major burden on society, significantly affecting millions of people and costing the populace billions annually. Despite major advances made to our understanding of pain, very few novel therapies have successfully translated to clinical care. A particular shortfall in this translation is due to the lack of a reliable, high-throughput, commercially available in vivo assay in rodents, particularly in mice. To address this deficit, we propose an innovative, automated, operant behavioral approach for assessing pain in rodents, with our long-range goal being the establishment of an operant model system that will quickly, systematically, and effectively evaluate pain. The central hypothesis is that operant assays can provide a sensitive, reliable, and clinically relevant way to evaluate sensory and nociceptive processing. One specific aim will be investigated: to evaluate a mouse operant model of thermal hyperalgesia and allodynia as compared to the rat operant model for studying pain. We will test this aim using an extremely innovative, automated, high-throughput approach for testing pain and analgesia in mice and rats. This includes using a reward-conflict strategy for assessing thermal pain. The rationale for the proposed research is that use of these operant assays in rats and mice to evaluate pain will provide a better method for future investigation of the mechanisms underlying pain disorders. This study explores an innovative approach for evaluating animal models of pain and would significantly advance the development of new treatments by providing a quick and reliable pain testing system using rodents. The product and process to be developed is an automated, user-friendly, investigator-independent, high-throughput, in vivo pain and analgesic testing system. We are particularly well-suited to complete this body of work, given the pairing of Stoelting Company's expertise in developing the product and Drs. Neubert and Caudle's pain-research experience. This line of research is significant because it explores a novel, high-throughput method to assess pain and pain relief following analgesic administration. If this line of research is successful, the result will have a significant impact on the way new pain-relieving therapies are screened and evaluated, ultimately allowing for a great reduction in the time for new drugs to become available clinically.