Brain Connectivity Patterns in Chronic Temporomandibular Joint Disorders

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Temporomandibular joint and muscle disorders (TMJD) are the most common cause of orofacial pain second only to tooth pain, for which effective treatment strategies remain empirical. Approximately 15% of acute TMJD patients will develop chronic pain, and some of these patients develop high pain-related disability that is associated with poor prognosis, even with treatment, and greater health care costs. Chronic TMJD pain pathophysiology includes dysregulation of brain circuits, and recent evidence suggests that connectivity patterns within the thalamocortical, antinociceptive, and corticolimbic brain circuits are associated with processing, modulation and persistence of pain. These brain circuits connectivity patterns have not been described in chronic TMJD patients and it is unknown if they can distinguish pain-related disability levels in patients. The overall objective of this proposal is to identify brain connectivity patterns that can differentiate chronic TMJD patients with high pain-related disability. To attain this objective, Dr. Moana-Filho will be trained under the mentorship of Dr. Christophe Lenglet in neuroimaging (primary mentor), Dr. David Bereiter in trigeminal neuroscience and Dr. Lynn Eberly in statistics. During the K99 mentored phase (Years 1-2; Aims 1 & 2), Dr. Moana-Filho will learn advanced analyzes of neuroimaging data from the NIH Human Connectome Project (HCP) (Aim 1) and will conduct a research study of chronic TMJD patients and pain-free controls using validated clinical phenotyping protocol, endogenous pain controls testing and multi-modal neuroimaging protocol developed by the HCP (Aim 2). Aim 1 will identify connectivity patterns within the thalamocortical, antinociceptive, and corticolimbic brain circuits as potential measures of sensory, modulatory, and emotional aspects of pain processing, respectively, from a large sample of healthy subjects from the HCP. Aim 2 will identify intrinsic connectivity patterns within these brain circuits as potential “signatures” for pain-related disability in chronic TMJD pain patients. During the R00 independent phase (Years 3-5; Aim 3), Dr. Moana- Filho will conduct a second study of chronic TMJD patients and matched controls to determine if evoked changes of connectivity patterns within those brain circuits evoked with noxious stimuli engaging endogenous pain controls can differentiate patients with high disability. The overall goal is to combine clinical sensory testing with psychosocial measures to enhance the precision and validity of brain imaging methods to differentiate subgroups of chronic pain patients. These newly developed brain-based signatures used along brief screening instruments are expected to guide clinicians and researchers in discriminating subgroups of chronic pain patients. The proposed training will support Dr. Moana-Filho career development as a dentist scientist dedicated to translational research in orofacial pain and is an initial step to achieve his long-term career goal of identifying brain-based signatures for transition of acute to chronic TMJD pain, supporting early identification of patients at risk for such transition and development of strategies to prevent it.