Operant Behavioral Instrument for Measuring Pain in Rodents

描述(申请人提供)：慢性疼痛仍然是社会的主要负担，每年严重影响数百万人，并造成民众数十亿美元的损失。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。这种翻译的一个特别缺陷是缺乏可靠的、高通量的、商业上可用的啮齿动物体内试验，特别是在小鼠身上。为了解决这一缺陷，我们提出了一种创新的、自动化的、可操作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快速、系统和有效地评估疼痛的可操作模型系统。中心假设是可操作性分析可以提供一种灵敏、可靠和临床相关的方法来评估感觉和伤害性信息的处理。一个特定的目标将被调查：评估热痛觉过敏和异位痛觉的小鼠可操作模型与用于研究疼痛的大鼠可操作模型的比较。我们将使用一种极其创新的、自动化的、高通量的方法在小鼠和大鼠身上测试疼痛和止痛，以测试这一目标。这包括使用奖励-冲突策略来评估热痛。这项拟议研究的基本原理是，在大鼠和小鼠中使用这些可操作的测试来评估疼痛将为未来研究疼痛障碍的机制提供更好的方法。这项研究探索了一种评估疼痛动物模型的创新方法，并将通过提供一种快速可靠的啮齿动物疼痛测试系统来显著推动新治疗方法的开发。将开发的产品和流程是一种自动化的、用户友好的、独立于研究人员的、高通量的体内疼痛和止痛测试系统。考虑到Stoelting公司在开发该产品方面的专业知识与Neubert博士和Caudle博士的疼痛研究经验相结合，我们特别适合完成这项工作。这项研究具有重要意义，因为它探索了一种新的、高通量的方法来评估疼痛和止痛后的疼痛缓解。如果这一系列研究成功，结果将对新的止痛疗法的筛选和评估方式产生重大影响，最终将大大缩短新药进入临床的时间。

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.