PSP Omics Center of Acute to Chronic Pain Signatures

项目总结 慢性疼痛目前是世界范围内一个重大且日益严重的卫生保健问题，其直接治疗方法 与阿片类药物和非类固醇抗炎药物的使用/滥用有关。然而，这种治疗努力是 普遍不足，因此努力了解慢性疼痛是如何演变的，特别是它从一个 急性疼痛事件，可以帮助提供更有效的治疗选择。此外，分子鉴定 与急性疼痛向慢性疼痛转化相关或预示从急性疼痛向慢性疼痛转化的信号将提供新的途径 阻止或减弱这种转变。尽管我们知之甚少，但我们确实认识到了某些途径的作用 在这种转化中的生理事件，包括但不限于神经源性炎症反应， 突触可塑性、胶质细胞激活和免疫细胞渗透及其相关的介质和细胞 受体相互作用。这些相关的信号分子和介体代表了广泛的 生化物种，即蛋白质、脂类、代谢物和胞外RNA，并且有证据表明 分子可以为慢性疼痛转化提供一种新的多分子信号。因此，总体目标是 这个PNNL-Stanford-Pittsburgh Omics数据生成中心(PSP-ODGC)是为了开发和实施HIGH 基于吞吐量组学的分析方法，用于量化与以下因素相关的广泛和多样化的分子参与者 急性疼痛到慢性疼痛的转换，目标是开发预测性信号并提供相关信息 分子机制。为了实现这一目标，我们正在将先进的质谱学 (Ms)多组学能力(太平洋西北国家实验室)、基因组学(Stanford Genome 技术中心)和高通量筛选能力(匹兹堡大学的Luminex Core 医学中心，UPMC)，以准确检测和量化广泛的预期目标。基于 我们之前在类似联盟中的丰富经验，即MoTrPAC(分子传感器) 体力活动联合会)，我们认识到初始规划阶段的重要性和所需的需求 以获得灵活的化验建议和开发。因此，我们也强烈强调我们战略的灵活性和 适应和满足项目需求的能力。总体而言，我们将促进沟通和互动 与MCC、CCC和DIRC一起简化样品处理/控制工作，以及时启动研究和 随后的分析。其次，提供了用于识别和量化的核心ODGC组件 双管齐下验证急、慢性疼痛转化分子特征的组学靶点 发现和有针对性的战略，其中有效的候选人将过渡到高通量分析平台 比如Luminex。第三，与DIRC整合努力，解决存储、流动和格式问题 定量分析数据和样本元数据以及下游信息学分析。

PROJECT SUMMARY Chronic pain is currently a substantial and growing health care issue worldwide, with its treatment directly associated with opioid and non-steroidal anti-inflammatory use/abuse. Such treatment efforts however are generally insufficient, hence efforts to understand how chronic pain evolves, specifically its conversion from an acute pain event, can help inform upon more effective therapeutic options. Moreover, identification of molecular signatures associated with or predictive of conversion from acute to chronic pain would provide new avenues to prevent or attenuate such conversion. Though poorly understood, we do recognize the role of certain pathways and physiological events in this conversion, including but not limited to neurogenic inflammatory responses, synaptic plasticity, glial activation, and immune cell infiltration, along with their associated mediators and cell receptor interactions. These associated signaling molecules and mediators represent a wide range of biochemical species, i.e., proteins, lipids, metabolites, and extracellular RNAs, and there is evidence that such molecules could provide a novel multi-molecular signature to chronic pain conversion. Thus, the overall objective of this PNNL-Stanford-Pittsburgh Omics Data Generation Center (PSP-ODGC) is to develop and implement high throughput omics-based assays for quantifying a broad and diverse set of molecular players associated with acute to chronic pain conversion with the goal to develop predictive signatures as well as inform upon relevant molecular mechanisms. To accomplish this objective, we are bringing together advanced mass spectrometry (MS) multi-omics capabilities (Pacific Northwest National Laboratory, PNNL), genomics (Stanford Genome Technology Center), and high throughput screening capabilities (Luminex Core at University of Pittsburgh Medical Center, UPMC) to accurately detect and quantify a broad spectrum of prospective targets. Based upon our extensive previous experience within similar consortium, i.e., the MoTrPAC (Molecular Transducers of Physical Activity Consortium), we recognize the importance of the initial planning phase and the required need for flexible assay proposals and development. Hence, we also strongly stress the flexibility in our strategy and capabilities to adapt and meet the needs of the program. Overall we will facilitate communication and interaction with the MCCs, CCC, and DIRC to streamline sample handling/control efforts for timely initiation of the study and subsequent analysis. Secondly, provide the core ODGC components for the identification and quantification of omics targets for the verification of molecular signatures of acute to chronic pain conversion using a two prong discovery and targeted strategy, where the valid candidates will transition to the high throughput assay platforms such as Luminex. Thirdly, integrate efforts with the DIRC in addressing the storage, flow, and format of the quantitative analysis data and sample metadata and downstream informatics analyses.