PROJECT SUMMARY A growing number of Americans – over 2 million – are affected by critical limb ischemia (CLI), the most severe expression of peripheral artery disease (PAD). CLI is an extremely painful condition characterized by ischemic pain, non-healing wounds or ulcers, or gangrenous tissues. While mortality and amputation burden is substantial, the majority of patients survives the year following diagnosis and more and more emphasis is being placed on shifting the focus of endpoints from avoiding limb loss and mortality to living with CLI and improving patients’ health status and quality of life. The majority of patients with CLI reports chronic pain, which may have a gre at impact on patients’ health status and quality of life. As CLI care is fragmented, with multiple specialties involved, concerted pain management efforts are lacking and amputation is often offered as one of the ways in which chronic pain is currently managed. Supported by insights based on the gate-control theory of pain, both medical and psychological interventions are effective options to manage chronic pain in medical populations. The phenomenology of pain, pain management approaches, and its impact on CLI outcomes, however, is poorly understood. The long-term goal of our program is to create an integrated, patient-centered, and multimodal pain management program for CLI. As a first step, we aim to study the medical pain management approaches of CLI over time, and its association with CLI outcomes across the lifespan. Specifically, we aim to examine the longitudinal patterns of pain medication utilization in CLI and PAD and its association with outcomes (readmission/amputation/depression/anxiety) in national claims-based datasets as well as in a Medicare linked national vascular registry. We hypothesize that the use of pain medications, including opioids, over time is higher in CLI than a control PAD (non-CLI) population; and that patterns of high opioid use differ by CLI intervention strategy (non-invasive, revascularization, or amputation); and that high opioid use in CLI and PAD is associated with a higher risk of readmission, amputation, mortality, and depression/anxiety. In addition, through the patient- centered SCOPE-CLI registry, we will study proxies of the HEAL common data elements through general structured equation models that will help provide insights as to how pain impacts related behavioral domains and functioning and treatment satisfaction. We hypothesize that more severe pain experiences, are associated with higher levels of depression, anxiety, distress, and worse health status and CLI treatment satisfaction. The empirical data generated from this program of research will identify current gaps in pain management strategies and interactions with CLI care, functioning, and outcomes that will further guide the design of future research on care innovations and the integration of holistic CLI pain management strategies.