Preclinical perspectives on disorders of the temporomandibular joint: Tracing the past, navigating the present, and shaping the future.
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2025-11
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Abstract
Temporomandibular disorders (TMDs) are complex conditions characterized by orofacial pain and dysfunction, affecting a significant portion of the population. TMDs may involve joint and/or muscle pain, dysfunction (e.g., noise, limited or altered jaw movements), or both, leading to a marked decrease in quality of life. Patients often experience functional limitations that hinder eating, speaking, and daily activities. Additionally, TMDs are frequently associated with psychological distress, including anxiety and depression, which further impacts overall well-being. Despite the profound individual and societal impact of TMDs, effective therapies remain elusive, partly due to deficiencies in translational research. A primary limitation in the TMD field is the scarcity of animal models that accurately replicate disease features in humans. This may ultimately be due to species differences, but likely also reflects the etiological and symptomatic heterogeneities of TMDs, as there are over 30 different conditions in this umbrella term. Both factors pose a significant challenge in developing and using animal models for TMD research. This review highlights preclinical TMD research to enhance clinical care, focusing on anatomy/physiology, pain and behavior models, functional and tissue modeling, biopsychosocial factors, and technological considerations. The "TMD Research Community" collaborated to produce this review, with the Discussion offering a proposal for a path forward.
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Neubert, John K, Kyle Allen, Tamara Alliston, Alejandro J Almarza, Kyriacos A Athanasiou, Basak Donertas-Ayaz, Bruna Balbino de Paula, Roxanne Bavarian, et al. (2025). Preclinical perspectives on disorders of the temporomandibular joint: Tracing the past, navigating the present, and shaping the future. The journal of pain, 36. p. 105560. 10.1016/j.jpain.2025.105560 Retrieved from https://hdl.handle.net/10161/33661.
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Scholars@Duke
Yong Chen
Dr. Yong Chen is an Associate Professor of Neurology at the Duke University School of Medicine. He is also affiliated with Duke Anesthesiology-Center for Translational Pain Medicine (CTPM) and Duke-Pathology.
The Chen lab mainly studies sensory neurobiology of pain and itch, with a focus on TRP ion channels and neural circuits. The main objective of our lab is to identify molecular and cellular mechanisms underlying chronic pain and chronic-disease associated itch, using a combination of animal behavioral, genetic, molecular and cellular, advanced imaging, viral, and optogenetic approaches. There are three major research areas in the lab: craniofacial pain, arthritis pain and joint function, and systemic-disease associated itch.
Katherine Martucci
Katherine Martucci Ph.D. is a neuroscientist who specializes in human clinical research of chronic pain, reward and motivation behaviors, sensory and acute pain perception, and opioid use and addiction. Dr. Martucci serves as Director of the Human Affect and Pain Neuroscience Lab which uses a combination of neuroimaging techniques, including functional magnetic resonance imaging (fMRI) of the brain and cervical spinal cord, as well as sensory, behavioral and psychological tests to study acute and chronic pain in humans.
As part of the Center for Translational Pain Medicine (CTPM), Dr. Martucci’s lab is part of Duke University’s Department of Anesthesiology, conducting research in collaboration with the Brain Imaging and Analysis Center (BIAC) and Duke Institute for Brain Sciences (DIBS).
Dr. Martucci earned her Ph.D. in Neurobiology and Anatomy at Wake Forest School of Medicine and continued her training in clinical research with a postdoctoral fellowship at Stanford University. While at Stanford, Dr. Martucci obtained a prestigious NIH K99 “Pathway to Independence Award”. Since joining Duke University in 2018, Dr. Martucci has acquired funding via multiple NIH grants to continue her line of neuroimaging clinical research of the central nervous system in chronic pain.
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.
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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