PROJECT SUMMARY / ABSTRACT Chronic pain impacts 20-30% of U.S. adults. Unfortunately, available pain treatments tend to be only moderately effective at best and many individuals cannot tolerate the associated adverse side effects. The use of opioid analgesics for treatment of chronic pain contributed, at least in part, to the current opioid crisis, affecting both individuals with pain and their family members and friends, and highlighting the need for the development of novel, non-addictive pain therapies. The NIH responded to this need by emphasizing the importance of high- quality clinical trials that incorporate novel biomarkers and endpoints in order to promote the development of effective pain therapies. To drive this effort, the NIH established the Early Phase Pain Investigation Clinical Network (EPPIC-Net) to provide a robust and readily accessible knowledgeable community and infrastructure for rapid design and performance of phase II clinical trials of pain treatments. The PI of this application is the MPI of the University of Rochester EPPIC-Net Specialized Clinical Center (UR EPPIC-Net), providing a unique opportunity to train mentees in the conduct of multisite pain clinical trials. Furthermore, the PI?s ongoing program of research addresses the need for condition-specific, clinically-meaningful outcome measures for pain trials and synergizes with EPPIC-Net efforts to (1) make valuable contributions to the field of clinical pain research and (2) offer a range of training opportunities in clinical pain research. The overall goal of this K24 proposal is to provide mentoring and research opportunities for junior investigators in order to increase the number of skilled clinical pain researchers who can design, conduct, analyze, and disseminate results of high-quality pain clinical trials, and in turn accelerate the development of novel therapies for chronic pain. Aim 1 will leverage the UR EPPIC- Net to train researchers on the necessary skills to conduct high-quality clinical trials for chronic pain therapies. Aims 2 and 3 are research projects focused on developing tools to improve clinical trials for 2 chronic pain conditions for which few effective therapies exist (i.e., chemotherapy-induced peripheral neuropathy (CIPN) and neurogenic intermittent claudication (NIC), a phenotypically-distinct, neuropathic chronic low back pain syndrome). Specifically, Aim 2 investigates the reliability and validity of measures of balance, lower limb sensation, and conditioned pain modulation for evaluating functional status or characterizing pain mechanisms in patients with CIPN. Aim 3 investigates the validity of clinically-relevant, accelerometry-based outcomes for NIC. Both of these aims leverage data from the PI?s current projects, providing efficient and valuable opportunities for the PI?s mentees to gain experience with data analyses, interpretation, and dissemination of clinical pain research findings via manuscripts and presentations. The K24 proposal outlines the PI?s plan for a highly collaborative and supportive research environment.