Nociplastic mechanisms in somatic and visceral pain

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PROJECT SUMMARY/ABSTRACT Chronic pain is a significant social and economic burden. Despite considerable progress over the last several decades of research, our understanding of the neurobiological underpinnings of chronic pain remains incomplete and this presents obstacles for improvement in pain management. Multimodal investigations into the mechanistic heterogeneity within and across chronic pain conditions are critical for the development of new and efficacious precision pain treatments. The central nervous system (CNS) governs the perception of pain. Sensitization of the CNS is a mechanism hypothesized to underly the increased pain and sensory sensitivity observed in patients with chronic pain. This mechanism is referred to as nociplastic pain. Quantitative sensory testing (QST), functional magnetic resonance imaging (fMRI), and patient-reported outcome measures (PROMs) are methods that can be used together to build multimodal profiles that characterize the degree and features of an individual’s nociplastic pain phenotype. The proposed F99 and K00 projects will use these methods to distinguish convergent and divergent nociplastic mechanisms across diagnostically distinct somatic (emanating from bones and soft tissue) and visceral (emanating from internal organs) chronic pain conditions. The overall objective for the proposed project is to identify shared and distinct nociplastic profiles between somatic and visceral pain conditions to ultimately stimulate the development of precision pain management tools. The goal of the F99 portion is to characterize sensory and neurobiological features of nociplastic pain in patients with somatic pain, including those with rheumatoid arthritis (RA), osteoarthritis (OA), and carpal tunnel syndrome (CTS), relative to healthy controls and patients with fibromyalgia – the archetypal nociplastic pain condition. This analysis will build a foundation for the long-term aim of this work’s K00 portion, where parallel sensory and neurobiological measures will be assessed in patients with visceral pain, including those with urologic chronic pelvic pain syndrome (UCPPS), overactive bladder (OAB), and gynecological chronic pelvic pain (CPP). Data from the NIDDK-funded Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network and Lower Urinary Tract Dysfunction Research Network (LURN) will be leveraged to complete the K00 project. Together, the mentoring and research activities of this F99 and K00 work will establish a career trajectory for me to become an independent researcher with expertise in urological pain.