Peripheral Artery Disease Pain Assessment and Interventions: Vascular Interventions and Biopsychosocial Evaluation - SUMMARY Peripheral artery disease (PAD) affects 230 million people globally, with chronic pain as a central symptom. Early stages involve claudication, severe stages, i.e., chronic limb-threatening ischemia (CLTI) involve ischemic rest pain, non-healing wounds, and gangrenous tissue. Effective pain management, cardiovascular risk management, wound healing, limb preservation, and quality of life improvement are crucial treatment goals. PAD pain is primarily seen as a macro-vascular perfusion issue, traditionally managed through peripheral vascular interventions (PVIs) and exercise. Disease staging relies on Rutherford stages based on macro- vascular information and pain experiences. Improving microvascular perfusion and tissue oxygenation through non-invasive quantification is essential. Our team has developed novel MRI protocols to evaluate blood flow, muscle and nerve microstructure, and metabolism, but how these translate to different pain phenotypes remains unknown. Ischemic damage alone does not fully explain PAD pain; physical, emotional, and behavioral factors also play significant roles. Advanced medical and psychological interventions manage chronic pain and offer safer alternatives to opioids. Our study aims to develop a biopsychosocial model for PAD pain, incorporating macro- and microvascular ischemic damage from novel MRI protocols, psychosocial and clinical profiles, and opioid use information. Using Bayesian methods, we will create a foundation for a future precision-medicine, multi- modal PAD pain management program. Aim 1: Over 12 months, we will study pain experiences, psychosocial variables, macrovascular information, comorbidities, and opioid usage in patients with Rutherford 1-6, using the existing multicenter, longitudinal PORTRAIT (n=1,275) and SCOPE-CLI (n=475) registries. We will develop pain phenotype clusters and explore high opioid usage, sex, race, and community distress interactions. We hypothesize stronger associations between psychosocial factors and chronic pain compared to macrovascular information, anticipating three pain clusters: emotional, uncomplicated ischemic, and complicated ischemic. Aim 2: We will correlate microvascular peripheral ischemia markers obtained at baseline, 6 months, and 12 months with biopsychosocial clinical profiles in 50 individuals with CLTI, derived from MRI protocols. We hypothesize that PAD pain experiences will correlate more strongly with psychosocial factors than microvascular ischemic damage, with more pronounced associations in opioid users. This work will lay the foundation for future mind-body intervention testing and the integration of precision- medicine approaches in PAD pain management.
