Phenotypic profile clustering pragmatically identifies diagnostically and mechanistically informative subgroups of chronic pain patients.
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2021-05
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Traditional classification and prognostic approaches for chronic pain conditions focus primarily on anatomically based clinical characteristics not based on underlying biopsychosocial factors contributing to perception of clinical pain and future pain trajectories. Using a supervised clustering approach in a cohort of temporomandibular disorder cases and controls from the Orofacial Pain: Prospective Evaluation and Risk Assessment study, we recently developed and validated a rapid algorithm (ROPA) to pragmatically classify chronic pain patients into 3 groups that differed in clinical pain report, biopsychosocial profiles, functional limitations, and comorbid conditions. The present aim was to examine the generalizability of this clustering procedure in 2 additional cohorts: a cohort of patients with chronic overlapping pain conditions (Complex Persistent Pain Conditions study) and a real-world clinical population of patients seeking treatment at duke innovative pain therapies. In each cohort, we applied a ROPA for cluster prediction, which requires only 4 input variables: pressure pain threshold and anxiety, depression, and somatization scales. In both complex persistent pain condition and duke innovative pain therapies, we distinguished 3 clusters, including one with more severe clinical characteristics and psychological distress. We observed strong concordance with observed cluster solutions, indicating the ROPA method allows for reliable subtyping of clinical populations with minimal patient burden. The ROPA clustering algorithm represents a rapid and valid stratification tool independent of anatomic diagnosis. ROPA holds promise in classifying patients based on pathophysiological mechanisms rather than structural or anatomical diagnoses. As such, this method of classifying patients will facilitate personalized pain medicine for patients with chronic pain.Type
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Gaynor, Sheila M, Andrey Bortsov, Eric Bair, Roger B Fillingim, Joel D Greenspan, Richard Ohrbach, Luda Diatchenko, Andrea Nackley, et al. (2021). Phenotypic profile clustering pragmatically identifies diagnostically and mechanistically informative subgroups of chronic pain patients. Pain, 162(5). pp. 1528–1538. 10.1097/j.pain.0000000000002153 Retrieved from https://hdl.handle.net/10161/30418.
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Scholars@Duke
Andrey V Bortsov
Dr. Andrey Bortsov is an Assistant Professor in the Department of Anesthesiology and holds a faculty position in the Center for Translational Pain Medicine (CTPM). He earned his Doctor of Medicine degree (1999) from Pavlov State Medical University, Saint Petersburg, Russia, and his PhD in Epidemiology (2010) from the University of South Carolina at Columbia.
In 2010, he joined the faculty at UNC Department of Anesthesiology as a Research Assistant Professor, where he studied genetics and non-genetic risk factors of chronic pain development after traumatic stressful events. Dr. Bortsov has published more than 30 peer-reviewed articles and presented his work at major and national and international conferences.
Dr. Bortsov joined the faulty at Duke University in 2016, where he continues his work on pain genomics. His major area of interest is application of novel computational and statistical methods to big genomic datasets to develop prediction models for disease risk and treatment outcomes.
Luda Diatchenko
Andrea Gail Nackley
Pain is a multidimensional sensory and emotional experience that is important for our survival, but once pain becomes chronic it is no longer beneficial and, instead, becomes a disorder in and of itself. Chronic pain remains one of our nation’s most significant healthcare problems due to a limited understanding of the underlying genetic and environmental factors. There are three main objectives of our lab’s research in this area:
- To determine the factors that put some people, but not others, at risk for maladaptive chronic pain conditions. To achieve this objective, we study genetic, biological, and environmental factors associated with the initial onset of pain as well as its severity and duration. In addition, we are beginning to study factors associated with patient-centered outcomes, which may have the power to predict optimal management strategies for different individuals.
- To elucidate the mechanism(s) whereby genetic, biological, and environmental factors drive chronic pain. To achieve this objective, we integrate molecular genetics, animal models, and clinical epidemiologic measures in order to reveal pathogenic processes that are unique to as well as common across a particular condition or individual(s). This line of inquiry will provide novel targets for the development of individualized therapeutics for the management of chronic pain.
- To improve pharmacologic management of pain. To achieve this objective, we conduct pre-clinical studies to test the efficacy of new compounds and to optimize the efficacy of existing compounds in patient-relevant animal models.
Aurelio A. Alonso
Dr. Alonso is an Associate Professor in the Department of Anesthesiology at Duke University School of Medicine and Director of Orofacial Pain at Duke Innovative Pain Therapies site located in the Brier Creek area of Raleigh, NC. Dr. Alonso is an internationally respected orofacial pain physician and is a Diplomate of the American Board of Orofacial Pain and Diplomate of the American Board of Dental Sleep Medicine, and a Fellow of the American Academy of Orofacial Pain. In addition, he is the only boarded Orofacial pain physician at Duke.
Dr. Alonso provides patients with innovative pain therapies as a member of the Center for Translational Pain Medicine (CTPM) team. The CTPM further expands Duke's existing clinical and research program in innovative pain therapies by bringing together leading basic scientists, clinicians, and clinical researchers. Dr. Alonso shares with the CTPM team the common core mission of unraveling the causes of painful conditions to better improve patient care. Dr. Alonso's focus area includes Orofacial pain, Temporomandibular disorders, headaches, Neuropathic Orofacial pain, and sleep disorder treatment.
Thomas Edward Buchheit
Dr. Buchheit serves as Director of the Regenerative Pain Therapies Program in the Duke Center for Translational Pain Medicine (CTPM), and practices Pain Medicine at both Duke University and the Durham VAMC. His research focus is on the local and systemic inflammatory mechanisms that drive pain in arthritis and nerve injury. He has led and participated in several multicenter research projects that have studied patients at Duke, the Durham VAMC, and Walter Reed National Military Medical Center, clarifying post-amputation pain phenotypes and mechanisms that drive the chronification of pain. These research pursuits have guided the clinical and translational programs of CTPM that strive develop biologically-based methods for the treatment of arthritis and degenerative musculoskeletal conditions. The program’s overarching goal is to move beyond opioids, steroids and anti-inflammatory medications for the treatment of pain.
Dr. Buchheit currently serves on the Editorial Board of Pain Medicine and recently completed service as Pain Medicine Division Chief in the Duke Department of Anesthesiology. He also serves on the Board of The Pain Society of the Carolinas and previously on the American Society of Anesthesiologists Pain Medicine Committee, (2012-2014), as an American Board of Anesthesiology Question Author (2011-2014), and President of Pain Society of the Carolinas (2015-2017).
Shad Benjamin Smith
Dr. Shad Smith is an assistant professor in the Department of Anesthesiology and holds a faculty position in the Center for Translational Pain Medicine (CTPM). Dr. Smith also has an adjunct appointment at the University of North Carolina at Chapel Hill, as part of the Center for Pain Research and Innovation (CPRI). He earned his bachelor’s degree in psychology with minors in chemistry and zoology from Brigham Young University, before moving on to graduate school.
In 2006, he graduated with a doctorate in psychology with an emphasis in behavioral neuroscience. Following his time at McGill, Dr. Smith accepted a post-doctoral fellowship in the CPRI at the UNC School of Dentistry. He received a Ruth L. Kirschstein National Research Service Award in 2008 to study the role of alpha adrenergic mechanisms in chronic orofacial pain. He joined the faculty at UNC as a research assistant professor in 2011. Dr. Smith has also served since 2007 as a research consultant, and since 2010 as the Director of Bioinformatics, for Algynomics, Inc., a Chapel Hill-based biotech firm spun off from research activities within the UNC School of Dentistry.
Dr. Smith joined the faculty at Duke University in 2016, where he continues his work with genetics of pain disorders. The primary focus of his research career has been the search for genetic variation that contributes to greater pain sensitivity and increased risk for chronic pain disease. He has worked for over a decade with genomic techniques, including both quantitative trait locus (QTL) mapping in the mouse and genetic association in human pain cohorts, investigating a number of pain-related diseases and phenotypes. Dr. Smith has published over 40 journal articles and book chapters, and presented his work at several international meetings. His work with projects such as the OPPERA (Orofacial Pain: Prospective Evaluation and Risk Assessment) study has resulted in a number of novel genes being recognized as genetic risk factors for pain.
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