PSP Omics Center of Acute to Chronic Pain Signatures

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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.