Motor Cortex as a Research & Therapeutic Target in TMD

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 their 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 μ-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 (muOR), have demonstrated that there is a decrease in μOR 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. We propose to demonstrate that acute (masseteric pain challenge) and chronic clinical pain measures in TMD patients are correlated with μ-opioid receptor (µOR) non-displaceable binding potential (BPND) in the thalamus and other pain-related regions.

Inclusion criteria

• Daily chronic TMD pain and dysfunction for at least one year (Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis I Group I: Myofascial pain diagnosis[15]) not adequately controlled by previous conventional therapies (TMJ open-surgery naïve) for more than

1 year

• Self-reported pain score of at least 3 on a 0-10 scale in spite of existing treatment in the two weeks preceding the onset of the study
• Taking stable doses of medications for at least 4 weeks (if taking medications), and willing to limit the introduction of new medications for chronic TMD symptoms during the study

Exclusion criteria

• Pain not primarily due to TMD
• History or current evidence of a psychotic disorder (e.g. schizophrenia) or substance abuse by DSM-IV criteria; bipolar or severe major depression
• History of neurological disorder (e.g. epilepsy, stroke, neuropathy, neuropathic pain)
• Any severe clinical condition that in the opinion of the principal investigator interferes with the study
• Pregnant or expecting to become pregnant during the study