TMJDIWG List of Research Opportunities and Needs Identified at Scientific Meetings in 2000-2004

1. Evaluate the biomechanics of the TMJ
2. Clarify vascular structure and blood flow in relation to the metabolic demand of joint tissue
3. Evaluate the role of proprioceptive feedback in regulating jaw muscle function
4. Exploration of the integration of proprioception and nociception in the pattern generator circuitry of chewing
5. Determine the form and function of the craniomandibular structures in human subjects
6. Characterize temporomandibular joint tissues
7. Differential regulation of motor units within the craniomandibular structures in human subjects

B. Pathophysiology & Biomarkers

1. Development of a TMJ Registry to provide the clinical information whereby appropriate questions can be addressed in the human populations
2. Study postnatal growth, maturation, and aging in the normal TMJ and in response to injury
3. Identification of the mechanisms of injury and disease
4. Develop diagnostic criteria based on validated physiologic models of TMJ disease
5. Pathophysiological pathway identification and development of therapeutic strategies
6. Study nerve-vascular interactions to gain insight into mechanisms regulating joint growth and repair
7. Compare the processes controlling postnatal joint homeostasis with prenatal joint development
8. Examination of the genetic risk factors that may be involved with TMJ disease
9. Genetic contribution of both connective tissue elements and immunological elements
10. Transcription factors that control the processes of ossification and the development of growth plate
11. Abnormal distribution of proteoglycans in TMJ cartilage of
    1. heterozygous cho mice
    2. Search for polymorphisms related to TMJ disorders
12. The role of crystalline Ca pyrophosphate dehydrate (CPPD) and basic Ca phosphate BCP in TMJs to determine if therapeutic approaches can be developed to modify the development of these phosphate crystals in TMJ disorders
13. Early identification of bone resorption (imaging)
14. Role of subchondral bone loss in natural history of TMJ
15. Cause(s) and effects that the accumulation of microdamage and trabecular microfractures in subchondral bone may play in joint degeneration
16. Angiogenesis role in TMJ disorders and development of arthritis in the joint
17. Role of various inflammatory cytokines that participate in the development of pain and tissue destruction in the TMJ
18. Role of cytokines and other inflammatory processes in TMJ muscles and joints during trauma
19. Role of growth factors in pathophysiology and treatment
20. Role of estrogen (both genomic and non-genomic effects) in pathophysiology, including potential interactions between estrogen and growth factors
21. Role of gender and hormonal regulatory systems
22. Central procession and integration of afferent input from craniofacial region with that from non-craniofacial regions, which directly or indirectly innervate the same CNS region (key to co-morbidity factors)
23. Presence and role of acid-sensitive ion channels in jaw muscles and other deep tissues of the craniofacial region
24. Mediators of angiogenesis in joints compared to other structures
25. Angiogenic markers
    1. Anti-angiogenesis agents offer therapeutic benefit in TMJ
    2. Gene knock out mice
26. Determine whether genetic susceptibility to angiogenesis plays a role in susceptibility to the TMJ and related musculature
27. Examine muscle fatigue, persistent craniofacial pain paradigms and the state-dependent nature of these stressors upon quality of sleep and CV disorders
28. Animal and clinical studies to examine the capacity of cardiopulmonary, carotid sinus and aortic arch baroreceptor systems to regulate pain, autonomic function, motor functions and sleep
29. Value of arthrocentesis should be evaluated as a diagnostic and therapeutic modality

C.  Pain

1. Role of glial cell activation and cytokine release in central and peripheral pathophysiology of craniofacial/deep tissue persistent pain
2. Relative role of central (including descending modulation) and peripheral plasticity (including effecter functions of afferent fibers) in mediating the onset of chronic pain in craniofacial regions
3. Changes in gene expression in the trigeminal ganglion, spinal cord, and brain in response to nociceptive stimuli using gene chip technology
4. Use of microarrays to determine what functional pathways may be responding to chronic pain
5. Elucidate peripheral mechanisms in TMJ pain
6. Elucidate the role of central mechanisms in TMJ pain
7. The origins and mechanisms responsible for pain in the masseter muscle of TMJ patients
8. The sensory neurons in masseter muscles and tendons to understand the origins of deep pain
9. Development of clinically relevant assays of nociception in human studies
10. Sensory, cognitive, affective, and other aspects of nociceptive stimulation on central processing (greater attention to sex and individual differences in response to nociceptive stimulation
11. Relative roles of central (including descending modulation) and peripheral plasticity (including effector functions of afferent fibers) in mediating the onset of chronic pain in craniofacial regions
12. Pro-inflammatory cytokines used as biomarkers of pain associated with TMJ injury
13. Studies are required to understand mechanisms of persistent TMJ pain and to develop biomarkers of pain
14. Pain imaging
15. Improve and develop diagnostic approaches and criteria for defining TMJ diseases
16. Basis of co-morbidity of pain disorders
17. Research NGF in synovial fluid

D. Changes in Cartilage

1. Turnover dynamics of the cartilage in a normal TMJ and that of patients with dysfunction
2. The role of apoptosis in cartilage degeneration of the TMJ needs to be explored
3. Regulation of the cartilage matrix turnover
4. Characterize the molecular structure of the TMJ – the proteoglycans and collagen types of all surface need to be determined

E. Co-Morbidities and Diagnostics

1. Unique features of arthritis in the TMJ
2. Role of osteoporosis as a co-risk
3. Obtain clinical details describing the co-phenotypes related to TMJ disorders
4. Accurate assessment and categorization of patients using standardized techniques to enable normalization of data to compare patients
5. Clinical trials to assess the risks and benefits of this therapy in blocking the production of TNF-alpha
6. Determine if human masseter muscle types vary with clinical characteristics and whether this is the cause of consequence of the various clinical problems found in patients with TMJ disease
7. Development of new invasive and non-invasive investigative tools (e.g. nano-sensors of muscle and nerve activity, for imaging of airway and esophageal passages, for chronic delivery of molecules modulating pathway functions related to sleep, respiration, the heart, and blood vessels) to assess TMJ muscle and joint function, neural pathways, swallowing, respiration and related cardiovascular functions (e.g. for imaging these pathways) are required.
8. Development of TMJ in normal and diseased states
9. Basic epidemiological data to systematically document the incidence and/or prevalence of CV and sleep-related consequence of TMJ
10. Prospective clinical studies to determine if TMJD constitute a risk factor for CV disease
11. Studies aimed at providing an understanding of the shared biomechanical aspects of patients with TMJD and sleep disordered breathing
12. Various therapeutic modalities to evaluate the effects on the progression of arthritis in the TMJ of the TNF alpha transgenic mouse

F. Treatment

1. Determine the effects of therapeutic drugs on tissue repair in temporomandibular diseases and disorders
2. Clarify tissue changes associated with foreign body reaction caused by alloplastic TMJ implants
   1. The value of hyaluronic acid injections need evaluated
   2. Management of oxidative stress associated with TMJ and associated muscles by biomechanical, biochemical and dietary approaches should be evaluated
   3. Examine cellular mechanisms underlying the reported in vivo effectiveness of chondroitin sulfate and glucosamine hydrochloride in human degenerative TMJ disorders
3. Effects of therapeutic drugs on tissue repair in temporomandibular diseases and disorders
4. Evaluate novel reconstruction methodologies for temporomandibular diseases and disorders
5. Explore the potential for protein and gene therapeutic approaches to temporomandibular repair
6. Develop evidence-based protocols for the management of myofacial pain (without joint involvement)
7. Determine whether or not therapeutic strategies that focus on modulating the activity of cytokines are efficacious in TMJ disease
8. Apply principles of tissue engineering using mesenchymal stem cells to regenerate bone, cartilage, muscle, marrow stroma, and tendon and develop ways to deliver them to repair or regenerate injured temporomandibular structures
9. Role of exercise (nature and timing) in inhibition of hyperalgesia

G. Animal Models

1. Animal models of OA to provide info about altered tissue composition or biomechanical properties and the pathways that are altered in cells
2. Develop new approaches and techniques using animal models to study the events associated with condylar resorption
3. TMJ pathology to develop experimental model systems to study underlying mechanisms of the disease
4. Consequences of changes in the masseter muscle strength and activity upon TMJ
5. Develop new model systems that better mimic the clinical features of craniofacial disorders, including those in which deep tissues are affected