Chronic temporomandibular joint disorders (TMD) represent clinical problems in which empirical treatments offer uncertain relief for a large number of patients. Many conventional therapies are ineffectual, leading to persistent treatment failure and/or poor iatrogenic-induced results;which raises the possibility that the cause for ther pain endurance may also lie in the brain milieu. Although MRI-based techniques have provided insights into some neuroplastic mechanisms of TMD in humans, many questions regarding its molecular mechanisms in vivo are still unanswered. First, how are endogenous mu-opioid mechanisms in the brain, known to be centrally involved in pain regulation, affected by acute and chronic TMD pain? Second, how can they be directly modulated to provide analgesic effect on pain measures? Finally, what are the neuroplastic effects in the brain after continuous modulation of those molecular mechanisms? The understanding of these processes is crucial to determine the mechanisms engaged in the persistence and, most important, the alleviation of TMD. Preliminary studies from our center, using positron emission tomography (PET) with [11C] carfentanil, a selective radiotracer for mu-opioid receptor (mu-OR), have demonstrated that there is a decrease in mu-OR availability (non-displaceable binding potential -BPND) in key pain-related structures in the brains of chronic trigeminal pain patients, which correlated with their clinical pain measures. Interestingly, a non-invasive and neuromodulatory tool, namely transcranial direct current stimulation (tDCS), can provide after-effect modulatory results on acute and chronic facial pain measures by changing activity of those key structures, including the activation of the endogenous mu-opioid neurotransmission. This proposed research utilizes a 3-step process: First, we will determine mu-opioid mechanisms mediating individual experiences in acute (experimental) and chronic (clinical) TMD pain states;Second, we will investigate the modulatory effect of 10 repetitive active and placebo tDCS sessions over the primary motor cortex (M1) on acute and chronic TMD pain measures;and Third, we will study whether repetitive M1-tDCS induces or reverts mu-ORBPND changes in the thalamus, and other pain-related structures, and if those changes are associated with modulation on acute and chronic TMD pain measures. This represents a change of paradigm, as we propose to directly target the same neuroplastic mechanisms under study by applying novel molecular neuroimaging and neuromodulatory protocols, reaching far beyond the traditional translational model.

Public Health Relevance

The frustration that conventional treatments fail to relieve symptoms in a large number of temporomandibular joint disorders (TMD) patients demonstrates that their chronic pain and dysfunction must in part be sustained by more than peripheral mechanisms in the symptomatic area (masticatory muscles and joint). We believe that chronic TMD may be induced by mal-adaptive changes in the endogenous mu-opioid mechanisms in the brain associated with pain processing and regulation. Our team of researchers will use novel neuroimaging and neuromodulatory techniques in TMD patients to identify and directly modulate such neuroplastic mechanisms that may be correlated with the persistence of their suffering.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
High Priority, Short Term Project Award (R56)
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Somatosensory and Chemosensory Systems Study Section (SCS)
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Kusiak, John W
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University of Michigan Ann Arbor
Schools of Dentistry
Ann Arbor
United States
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Cummiford, Chelsea M; Nascimento, Thiago D; Foerster, Bradley R et al. (2016) Changes in resting state functional connectivity after repetitive transcranial direct current stimulation applied to motor cortex in fibromyalgia patients. Arthritis Res Ther 18:40
Donnell, Adam; D Nascimento, Thiago; Lawrence, Mara et al. (2015) High-Definition and Non-invasive Brain Modulation of Pain and Motor Dysfunction in Chronic TMD. Brain Stimul 8:1085-92