in degenerative joint diseases, the articiilating surfaces of a joint are gradually destroyed, ultimately resulting in pain and joint dysfunction. Most degenerative joint diseases are chronic pathologies: that are ? driven by disease processes occurring over years, and while end-stage disease can be described by cartilage loss, subchondral bone remodeling, dysfunction, and pain, the initiating stages do not always have a clear etiology. As a result, disease modifying strategies are faced with a diverse blend of chronic disease processes that have potentially risen from a number of cbhnplex origins. The goal of the ROO phase of this K99/R00 application is to Investigate local regulation of catabolic and pro-inflammatory mediators in the rat temporomandibular joint (TMJ) and the subsequent development of pain related behaviors and TMJ dysfunction. This work represents the transition of a K99/R00 award to the independent ROO phase. During K99 training, the PI investigated the local regulation of disease factors associated with knee arthritis and developed new quantitative gait measures of knee dysfunction for the rat pre-clinical model. In the ROO phase, a similar approach is proposed for the study of degenerative! pathology in the TMJ. First, we will develop new methods to assessib^haviors associated with TMJ pain and dysfunction in the rat, including new systems to assess chewing kjhematics, dietary habits,^ bite-force, sleeping and grooming behaviorSi and orofacial sensitivity. Concurrently, we will develop a model of chronic TMJ degeneration using ihtra-articular injection of sodium monoioddacetate (MIA);here, TMJ degeneration induced by MIA will occur over a period of weeks, simulating .the Chronic cascade of TMJ arthritis, in this model, we will investigate catabolic and pro-imflammatory rriarkers of TMJ pathology in thes serum, saliva, and TMJ synovial fluid. F'ihally, we will combine behavioral analysis tools with our model;of TMJ degeneration to examine tliei relatidnship between local regulation of disease processes and the development of disease sequelae associated with TMJ degeheration. With this work, we aim to identify critical features, stages,/and; mediators of TMJ degeheration with the goal of developing future interventional studies.
; TMJ (jaw) disorders are the 2nd most common musculoskeletal condition that results in chronic pain and disability. These disorders affect 5-12% of the population with an annual cost of $4,000,000,000, according to NIDCR health statistics. The goal of this proposal Is to develQp research tools that will improve our understanding how of temporomandibular joint disorders develop and progress.
|Garraud, Alexandra; Velez, Camilo; Shah, Yash et al. (2016) Investigation of the Capture of Magnetic Particles From High-Viscosity Fluids Using Permanent Magnets. IEEE Trans Biomed Eng 63:372-8|
|Lakes, E H; Allen, K D (2016) Gait analysis methods for rodent models of arthritic disorders: reviews and recommendations. Osteoarthritis Cartilage 24:1837-1849|
|Yarmola, Elena G; Shah, Yash; Arnold, David P et al. (2016) Magnetic Capture of a Molecular Biomarker from Synovial Fluid in a Rat Model of Knee Osteoarthritis. Ann Biomed Eng 44:1159-69|
|Kloefkorn, Heidi E; Pettengill, Travis R; Turner, Sara M F et al. (2016) Automated Gait Analysis Through Hues and Areas (AGATHA): A Method to Characterize the Spatiotemporal Pattern of Rat Gait. Ann Biomed Eng :|
|Rohrs, Eric L; Kloefkorn, Heidi E; Lakes, Emily H et al. (2015) A novel operant-based behavioral assay of mechanical allodynia in the orofacial region of rats. J Neurosci Methods 248:1-6|
|Jacobs, Brittany Y; Kloefkorn, Heidi E; Allen, Kyle D (2014) Gait analysis methods for rodent models of osteoarthritis. Curr Pain Headache Rep 18:456|
|Hwang, Priscilla Y; Allen, Kyle D; Shamji, Mohammed F et al. (2012) Changes in midbrain pain receptor expression, gait and behavioral sensitivity in a rat model of radiculopathy. Open Orthop J 6:383-91|
|Allen, Kyle D; Mata, Brian A; Gabr, Mostafa A et al. (2012) Kinematic and dynamic gait compensations resulting from knee instability in a rat model of osteoarthritis. Arthritis Res Ther 14:R78|
|Allen, Kyle D; Adams Jr, Samuel B; Mata, Brian A et al. (2011) Gait and behavior in an IL1Î²-mediated model of rat knee arthritis and effects of an IL1 antagonist. J Orthop Res 29:694-703|
|Allen, Kyle D; Shamji, Mohammed F; Mata, Brian A et al. (2011) Kinematic and dynamic gait compensations in a rat model of lumbar radiculopathy and the effects of tumor necrosis factor-alpha antagonism. Arthritis Res Ther 13:R137|