Developing Radiocaine NaV imaging as a response monitoring biomarker for chronic pain

摘要/摘要 目前还没有能够客观测量疼痛信号的生物标志物或工具。从历史上看，疼痛 人类已经使用主观评级量表进行了测量，以确定其存在和严重程度。在动物身上 根据疼痛模型，疼痛是通过观察疼痛行为的半定量方法来测量的。尽管 有用的是，这些措施固有的主观性质阻碍了研究和治疗努力。 据估计，仅在美国，慢性疼痛每年的经济负担就超过8000亿美元，其中大部分 因为疼痛管理不当需要不成比例的更多医疗资源。同样，临床 在所有神经系统适应症中，疼痛疗法的试验是最昂贵的，成功率也是最低的。 管理慢性疼痛的困难导致了阿片类药物的流行，因为许多人转向处方止痛药 作为一种缓解手段，但最终往往会上瘾并求助于更有效和更危险的阿片类药物 因为他们的容忍度增加了。放射性卡因是一种新型的正电子发射断层扫描(PET)显像剂 正在发展成为一种生物标记物，以解决疼痛护理和治疗开发中的问题。我们最近 在神经病理性疼痛的啮齿动物模型中发表的研究结果证明了定位疼痛生成器的能力 快速、准确、客观地测量其信号强度。我们的最终目标是：1)改变 评估(实验性)疼痛治疗，以及2)通过分子评估疼痛评估中的护理标准 成像。疼痛成像生物标记物技术的使用将允许客观的疗效数据(临床前 和临床试验中)，并通过由于更同质的总体而实现更小的样本量来降低成本， 即具有特定的“疼痛信号”，并更准确地测量止痛效果。拟议的研究将 在早期临床试验中评估放射性卡因。成功的结果将为临床应用试验奠定基础 这进一步将这一有希望的方法发展成一种有用的生物标记物，用于改变疼痛护理。

Summary/Abstract There are currently no biomarkers or tools capable of objectively measuring pain signals. Historically, pain in humans has been measured using subjective rating scales to determine its 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. The annual economic burden of chronic pain is estimated to exceed $800 billion in the USA alone, largely because inadequately managed pain requires disproportionately more healthcare resources. Similarly, clinical trials for pain therapies are the most expensive, and have the lowest success rate, of all neurological indications. Difficulty managing chronic pain has led to the opioid epidemic as many individuals turn to prescription painkillers as a means of relief, but often end up becoming addicted and resorting to more potent and dangerous opioids as their tolerance increases. Radiocaine is a novel positron emission tomography (PET) imaging agent that we are developing as a biomarker to address the issues in pain care and therapy development. Our recently published findings in a rodent model of neuropathic pain demonstrate the ability to localize the pain generator rapidly and accurately and objectively measure its signal intensity. 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 use of pain imaging biomarker 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. The proposed study will evaluate Radiocaine in early-stage clinical trials. Successful results will set the stage for applied clinical trials that further develop this promising approach into a useful biomarker for transforming pain care.