PROJECT ABSTRACT While localized primary pain conditions are prevalent in youth, a significant subset of these patients experience multiple pain conditions and meet the criteria for chronic overlapping pain conditions (COPCs). COPCs have a marked negative impact on daily functioning and quality of life in youth and carry a high risk for continued pain and disability into adulthood. The underlying factors contributing to the development and persistence of COPCs in youth are unknown. The current proposal offers an innovative and previously unexplored approach to determine whether disruptions in spatial (concurrent noxious stimuli across the body) and temporal (noxious stimuli presented over time) filtering of nociceptive processing, reflecting pain amplification (e.g., increased facilitation and/or reduced inhibition), contribute to COPCs. Several quantitative sensory testing methods are uniquely positioned to probe disruptions in nociceptive filtering across spatial (spatial summation, SS; conditioned pain modulation, CPM) and temporal (temporal summation, TS; offset analgesia, OFA) domains. Our recent pilot studies found evidence for greater disruptions in spatial (CPM) and temporal (TS) filtering in youth with COPCs. Our primary objective is to determine if spatial and temporal filtering of nociceptive information differentiates youth with COPCs from those with localized pain and healthy controls and determine whether distinct profiles of disrupted nociceptive processing are associated with the transition of localized pain to COPCs. To accomplish this, the current study will leverage expertise and a vast clinical infrastructure (Migraine, Gastroenterology, Rheumatology and Pain Management clinics) at a large pediatric medical center to enroll 140 youth with a localized pain condition (migraine, abdominal pain, local MSK), and 140 youth with COPC’s. We will also recruit 140 healthy youth to serve as a control group. Following initial phenotyping to delineate disruptions in spatial and temporal dimensions of nociceptive processing (Aim 1), participants will be assessed for changes in pain status (localized to COPCs) every three months for one year (Aim 2). In Aim 1, we hypothesize that youth with COPCs will show disrupted spatial (reflected by reduced CPM and enhanced SS) and temporal (reflected by enhanced TS and reduced OFA) processing compared to youth with localized pain and healthy controls. These findings will delineate specific disruptions of nociceptive processing in patients with COPCs. For Aim 2, we hypothesize that a subset of youth with localized pain and disrupted spatial and temporal filtering will develop COPCs. We will examine the stability of spatial and temporal filtering at clinically relevant time points (3-, 6-, and 12-months). We will also explore whether other factors, including concomitant treatments, influence the disrupted filtering and the transition to COPCs. Our research will provide the first insight into the presence and impact of disrupted nociceptive filtering related to COPCs and its naturalistic progression from localized pain. This information will be critical in identifying risk patterns that can be useful in the prevention of progression to COPCs and mitigating long-term risk.

PROJECT NARRATIVE The proposed research will provide critical new information about the presence and impact of disrupted spatial and temporal nociceptive processing in youth with localized chronic pain and chronic overlapping pain conditions (COPCs). The study will also provide insight into which individuals are more likely to transition from a single pain condition to COPCs, providing an opportunity for early identification by screening for disrupted nociceptive processing and prioritization of these at-risk patients for intensive care, multidisciplinary therapy. Leveraging the current study, our long-term objectives are to reduce the development of COPCs, which closely aligns with the NIH’s Federal Pain Research Strategy and National Institute of Neurological Disorders and Stroke (NINDS) to reduce the public health burden of chronic pain across the lifespan.