Operant Behavioral Instrument for Measuring Trigeminal Neuropathic Pain in Rodent

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，但很少有新疗法成功地转化为临床护理。这种翻译的一个特别不足是缺乏高通量的、可商购的体内测定。为了解决这一缺陷，我们正在改进我们的新的操作性行为系统，用于评估啮齿动物的疼痛。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。本研究将探讨三个特定目标：（1）评估用于操作性疼痛测试的珀耳帖热刺激系统;（2）开发和优化操作性疼痛测试系统的软件控制;（3）评估多联操作性行为盒单元。我们将使用我们在第一阶段赠款中开发的创新操作系统来实现这些目标，该系统以奖励冲突范式评估热疼痛。所提出的研究的基本原理是，软件驱动的体内系统将允许高通量方法来完成行为疼痛和镇痛研究。我们正在开发一种创新产品并将其商业化，以满足这些需求。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。我们完成了第一阶段提案的所有里程碑，第二阶段赠款将建立在我们的成功之上。该产品线可以显著减少筛选和评估新的止痛疗法的时间，大大提高发现上级止痛剂的机会。 公共卫生相关性：这种可靠的、高通量的操作性疼痛评估设备的成功开发将通过学术和制药机构带来商业上的成功。这种商业化将创造一种方法，更快地将新的可行的疼痛治疗方法从实验室转移到床边;如果这有助于加速一种新的有效的镇痛治疗，将产生巨大的社会效益。该项目将为实现推进翻译疼痛研究的目标迈出关键一步。

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 new therapies have successfully translated to clinical care. A particular shortfall in this translation is the lack of a high-throughput, commercially available in vivo assay. To address this deficit, we are refining our novel operant behavioral system for assessing pain in rodents. The central hypothesis is that operant assays can provide a sensitive, reliable, and clinically relevant way to evaluate sensory and nociceptive processing. Three specific aims will be investigated: (1) to evaluate a peltier thermal-stimulus system for operant pain testing; (2) to develop and optimize the software control of the operant pain-testing system; and (3) to evaluate multiple-linked operant behavior box units. We will achieve these aims using the innovative operant system that we developed in the Phase I grant, which assesses thermal pain in a reward-conflict paradigm. The rationale for the proposed research is that a software-driven, in vivo system will allow for a high- throughput approach for completing behavioral pain and analgesic studies. We are developing and commercializing an innovative product that will meet these needs. We are particularly well suited to complete this work, given the pairing of Stoelting Company's expertise in developing the product and Drs. Neubert and Caudle's pain-research experience. We completed all of the Phase I proposal's milestones, and this Phase II grant will build on our success. This product line could significantly reduce the time for new pain-relieving therapies to be screened and evaluated, greatly enhancing the opportunity for discovery of a superior analgesic. PUBLIC HEALTH RELEVANCE: Successful development of this reliable, high-throughput operant pain-assessment device would lead to commercial success through both academic and pharmaceutical institutions. This commercialization would create a method to more quickly convey new viable pain treatments from bench to bedside; if this helped accelerate even one new effective analgesic therapy, there would be tremendous societal benefit. This project will provide a key step in reaching this goal of advancing translational pain research.