Developing EXP-1801 as an imaging agent to quantify pain and analgesia

摘要/摘要 目前还没有工具可以客观地测量疼痛。从历史上看，人类的疼痛 使用主观评级来确定存在性和严重性。在动物模型中，疼痛是通过 依赖于疼痛行为观察的半定量分析。虽然有用，但本质上 这些措施的主观性质阻碍了研究和治疗工作。简单地说，不准确 疼痛测量导致不准确的疼痛管理。过度治疗和对止痛药上瘾是 在美国持续流行的慢性疼痛的估计经济负担估计超过600美元 亿客观疼痛测量技术的一个优点是降低成本。平均治疗费用 慢性或神经性疼痛患者每年19，000美元。这些费用被夸大了，因为许多病人 对疼痛的管理不足，这需要不成比例的更多资源。的很大一部分 这些费用支付给没有经历实质性疼痛的患者，例如滥用阿片类药物的患者。 另一个可以大幅降低成本的领域是药物开发。平均疼痛临床试验 成本约为7100万美元。疼痛成像技术的使用将允许客观的疗效数据（两者都是）。 临床前和临床试验中），并通过实现更小的样本量来降低成本， 同质群体;即具有特定的"疼痛信号"，并且更准确地测量镇痛药浓度。 方面的影响. 我们最近发明了一种新的正电子发射断层扫描（PET）成像剂，我们开发的工具， 以解决疼痛护理和治疗发展中的这些问题。虽然PET检测的能力 用于（早期）疾病检测的病理变化广泛用于癌症和神经系统疾病， 尚未用于疼痛适应症。我们已经在健康的大鼠和非人类灵长类动物中测试了这种分子 在神经组织中发现了很强的信号背景比我们的最终目标是：1）改变 （实验性）疼痛治疗的评价，和2）通过分子生物学评估疼痛的护理标准 显像 这项研究旨在确定我们的成像剂客观测量疼痛的可行性， 啮齿动物这将为II期研究奠定基础，该研究将进一步将该药物开发为量化 疼痛/镇痛。

Summary/Abstract There are currently no tools available that can objectively measure pain. Historically, pain in humans has been measured using subjective ratings to determine presence and severity. In animal models, pain is measured by semi-quantitative assays that rely on the observation of pain behaviors. Though useful, the inherently subjective nature of these measures has hampered both research and treatment efforts. Simply put, inaccurate pain measurement leads to inaccurate pain management. Overtreatment and addiction to pain medications are a continuing epidemic in the U.S. The estimated economic burden of chronic pain is estimated to exceed $600 billion. One advantage of an objective pain measuring technology is cost reduction. The average cost to treat a chronic or neuropathic pain patient is $19,000 per year. These costs are exaggerated because many patients have inadequately managed pain, which requires disproportionately more resources. A significant portion of these costs go to patients who are not experiencing substantial pain; e.g. those who abuse opioids. Another area where costs could be significantly reduced is in drug development. The average pain clinical trial cost is around $71 million. The use of a pain imaging technology would allow for objective efficacy data (both pre-clinically and in clinical trials), and reduce costs by enabling smaller sample sizes due to more homogeneous populations; i.e. with a particular “pain signal,” and more accurate measurement of analgesic effects. We recently invented a novel positron emission tomography (PET) imaging agent that we developing as a tool to address these issues in pain care and therapy development. Although the ability of PET to detect pathological changes for (early) disease detection is widely used in cancer and neurological diseases, it has not yet been used for pain indications. We have tested this molecule in healthy rats and non-human primates and found a strong signal to background ratio in nerve tissue. Our ultimate goals are: 1) to change the evaluation of (experimental) pain therapies, and 2) the standard of care in pain assessment through molecular imaging. The proposed study is designed to determine the feasibility of our imaging agent to objectively measure pain in rodents. This will set the stage for a Phase II study that further develops this agent into a tool for quantifying pain/analgesia.