PSP Omics Center of Acute to Chronic Pain Signatures

项目摘要 慢性疼痛是目前世界范围内一个重要的和日益增长的卫生保健问题，其治疗直接 与阿片类和非甾体抗炎药使用/滥用相关。然而，这种治疗努力 一般不充分，因此努力了解慢性疼痛是如何演变的，特别是它从慢性疼痛的转化。 急性疼痛事件，可以帮助提供更有效的治疗方案。此外，分子鉴定 与急性疼痛向慢性疼痛的转化相关或预测性的特征将提供新的途径， 防止或减弱这种转化。虽然我们对它的了解很少，但我们确实认识到某些途径的作用， 以及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、神经胶质活化和免疫细胞浸润，沿着它们相关的介质和细胞 受体相互作用这些相关的信号分子和介质代表了广泛的 生物化学物种，即，蛋白质、脂质、代谢物和细胞外RNA，并且有证据表明， 分子可以为慢性疼痛转化提供新的多分子标记。因此，总体目标 这个PNNL-Stanford-Pittsburgh组学数据生成中心（PSP-ODGC）的任务是开发和实现高 基于组学的通量分析，用于量化与以下相关的广泛而多样化的分子参与者 急性到慢性疼痛的转换，目标是开发预测性特征，并告知相关的 分子机制为了实现这一目标，我们将先进的质谱技术 (MS)多组学能力（太平洋西北国家实验室）、基因组学（斯坦福大学基因组 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），以准确地检测和量化广泛的预期目标。基于 我们之前在类似财团中的丰富经验，即，MoTrPAC（分子传感器） 身体活动联盟），我们认识到初始规划阶段的重要性和所需的需求 用于灵活的分析方案和开发。因此，我们还大力强调我们战略的灵活性， 适应和满足项目需求的能力。总的来说，我们将促进沟通和互动 与MCC、CCC和DIRC一起简化样本处理/控制工作，以便及时启动研究， 后续分析。其次，提供核心ODGC组分，用于鉴定和定量 组学靶点用于验证使用双管齐下的急性至慢性疼痛转换的分子特征 发现和靶向策略，其中有效候选物将过渡到高通量测定平台 例如Luminex。第三，与DIRC一起努力解决数据的存储、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.