Preclinical perspectives on disorders of the temporomandibular joint: Tracing the past, navigating the present, and shaping the future

John K Neubert; Kyle Allen; Tamara Alliston; Alejandro J Almarza; Kyriacos A Athanasiou; Basak Donertas-Ayaz; Bruna Balbino de Paula; Roxanne Bavarian; Nidhi Bhutani; Brian E Cairns; Robert M Caudle; Yang Chai; Jian-Fu Chen; Yong Chen; Glenn T Clark; Yenisel Cruz-Almeida; Alexandre F DaSilva; Paul L Durham; Airam Vivanco Estela; Millie Embree; Roger Fillingim; Fernando Guastaldi; Shruti Handa; Sunil D Kapila; David Keith; Keith L Kirkwood; Phillip Kramer; Katherine T Martucci; Niall P Murphy; Andrea G Nackley; Richard Ohrbach; Benedikt Sagl; Shad B Smith; Feng Tao; Beth Winkelstein; Hai Yao; Simon Young; Michael S Gold

doi:10.1016/j.jpain.2025.105560

Preclinical perspectives on disorders of the temporomandibular joint: Tracing the past, navigating the present, and shaping the future

J Pain. 2025 Nov:36:105560. doi: 10.1016/j.jpain.2025.105560. Epub 2025 Sep 13.

Authors

John K Neubert¹, Kyle Allen², Tamara Alliston³, Alejandro J Almarza⁴, Kyriacos A Athanasiou⁵, Basak Donertas-Ayaz⁶, Bruna Balbino de Paula⁷, Roxanne Bavarian⁸, Nidhi Bhutani⁹, Brian E Cairns¹⁰, Robert M Caudle¹¹, Yang Chai¹², Jian-Fu Chen¹², Yong Chen¹³, Glenn T Clark¹², Yenisel Cruz-Almeida¹⁴, Alexandre F DaSilva¹⁵, Paul L Durham¹⁶, Airam Vivanco Estela⁷, Millie Embree¹⁷, Roger Fillingim¹⁴, Fernando Guastaldi⁸, Shruti Handa⁸, Sunil D Kapila¹⁸, David Keith⁸, Keith L Kirkwood¹⁹, Phillip Kramer⁶, Katherine T Martucci²⁰, Niall P Murphy⁶, Andrea G Nackley²¹, Richard Ohrbach²², Benedikt Sagl²³, Shad B Smith²⁰, Feng Tao⁶, Beth Winkelstein²⁴, Hai Yao²⁵, Simon Young²⁶, Michael S Gold²⁷

Affiliations

¹ Department of Biomedical Sciences, College of Dentistry, Texas A&M University, Dallas, TX, USA; McKnight Brain Institute, University of Florida, 1149 Newell Dr, Gainesville, FL 32610, USA. Electronic address: jneubert@tamu.edu.
² Department of Biomedical Engineering, University of Florida, Gainesville, FL 32610, USA.
³ Department of Orthopaedic Surgery, University of California San Francisco, San Francisco, CA, USA.
⁴ Department of Oral and Craniofacial Sciences, Center for Craniofacial Regeneration, University of Pittsburgh, Pittsburgh, PA, USA.
⁵ Department of Biomedical Engineering, University of California, Irvine, CA, USA.
⁶ Department of Biomedical Sciences, College of Dentistry, Texas A&M University, Dallas, TX, USA.
⁷ Department of Oral & Maxillofacial Surgery, University of Florida, Gainesville, FL 32610, USA.
⁸ Department of Oral & Maxillofacial Surgery, Massachusetts General Hospital, Harvard School of Dental Medicine, Boston, MA, USA.
⁹ Department of Orthopaedic Surgery, Stanford University, Palo Alto, CA, USA.
¹⁰ Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
¹¹ Department of Oral & Maxillofacial Surgery, University of Florida, Gainesville, FL 32610, USA; McKnight Brain Institute, University of Florida, 1149 Newell Dr, Gainesville, FL 32610, USA.
¹² Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, USA.
¹³ Departments of Neurology, Anesthesiology, and Pathology, Duke University School of Medicine, Durham, NC 27710, USA.
¹⁴ Department of Community Dentistry & Behavioral Science, University of Florida, Gainesville, FL, USA.
¹⁵ Department of Biologic & Materials Sciences, University of Michigan, Ann Arbor, MI, USA.
¹⁶ Department of Biology, Missouri State University, Springfield, MO 65806, USA.
¹⁷ Department of Orthodontics, Columbia University, New York, NY, USA.
¹⁸ Department of Orthodontics, University of California Los Angeles, Los Angeles, CA, USA.
¹⁹ Department of Oral Biology, University at Buffalo, Buffalo, NY, USA.
²⁰ Center for Translational Pain Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, NC 27710, USA.
²¹ Center for Translational Pain Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA.
²² Department of Oral Diagnostic Sciences, University at Buffalo, Buffalo, NY, USA.
²³ University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria.
²⁴ Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
²⁵ Department of Bioengineering, Clemson University, USA.
²⁶ Department of Oral Maxillofacial Surgery, University of Texas Houston, Houston, TX, USA.
²⁷ Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA.

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.

Keywords: Biomechanics; Biopsychosocial model; Orofacial pain; Preclinical models; Temporomandibular disorder (TMD).

Publication types

Review

MeSH terms

Animals
Disease Models, Animal*
Facial Pain* / etiology
Facial Pain* / physiopathology
Humans
Temporomandibular Joint Disorders* / physiopathology

Abstract

Publication types

MeSH terms

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