Proteomic signature of Temporomandibular Joint Disorders (TMD): Toward diagnostically predictive biomarkers

Abstract

The temporomandibular joint (TMJ) articulates the mandible with the maxilla. Temporomandibular joint disorders (TMD) are dysfunctions of this joint, which range from acute to chronic inflammation, trauma and dislocations, developmental anomalies and neoplasia. TMD manifest as signs and symptoms that involve the surrounding muscles, ligaments, bones, synovial capsule, connective tissue, teeth and innervations proximal and distal to this joint. TMD induce proximal and distal, chronic and acute, dull or intense pain and discomfort, muscle spasm, clicking/popping sounds upon opening and closing of the mouth, and chewing or speaking difficulties. The trigeminal cranial nerve V, and its branches provide the primary sensory innervation to the TMJ. Our clinical work suggests that the auriculotemporal (AT) nerve, a branch of the mandibular nerve, the largest of the three divisions of the trigeminal nerve, plays a critical role in TMD sequelae. The AT nerve provides the somatosensory fibers that supply the joint, the middle ear, and the temporal region. By projecting fibers toward the otic ganglion, the AT nerve establishes an important bridge to the sympathetic system. As it courses posteriorly to the condylar head of the TMJ, compression, injury or irritation of the AT nerve can lead to significant neurologic and neuro-muscular disorders, including Tourette's syndrome,Torticolli, gait or balance disorders and Parkinson’s disease. Here, we propose that a proteomic signature of TMD can be obtained by assessing certain biomarkers in local (e.g., synovial fluid at the joint) and distal body fluids (e.g., saliva, cerebrospinal fluid), which can aid TMD diagnosis and prognosis.

Stakeholder engagement analysis - a bioethics dilemma in patient-targeted intervention: patients with temporomandibular joint disorders

“…In our previous studies, we showed that TMD contributes to the development and exacerbation of cervical dystonia and other movement disorders, most likely via neuritis of the auriculotemporal branch of the trigeminal nerve that feeds into the pontine region and controls head and body posture [ 5 ]. In those studies we also proposed that the proteomic signature of biomarkers in local (e.g., joint synovial fluid) and distal body fluids (e.g., saliva, cerebrospinal fluid) in a translational research modality would behoove patient-targeted TMD diagnosis and prognosis [ 6 , 7 ]. Our data obtained within the EBD-PBRN also indicated remarkable elevations in certain neuroimmune factors in the synovial fluid of TMD patients that were significantly and positively correlated with diagnostic imaging-rated severity of the TMD condition [ 8 ] (Barkhordarian et al, under review) confirming the intimate coexistence of neuroimmunological and neuropathology complexities with TMD.…”

Translational Healthcare Can Prevent Ambulatory Diagnostic Failures

“…The broad nature of these criteria leads to a significant risk of diagnostic failure [4,5]. Improved diagnosis by means of detailed translational research protocols (e.g., characterization of molecular profile of synovial inflammation -viz., by translational research protocols -is therefore timely and critical [6,7].…”

Translational research of temporomandibular joint pathology: a preliminary biomarker and fMRI study

“…Recent studies show that neurological disorders, such as Parkinson's Disease, Cervical Dystonia, Tourette's syndrome may have a root cause in TMJ related disorders. Undiagnosed TMJ disc dislocation such as distal condylar displacement and associated compression/irritation of the AT nerve may be due to bone loss, trauma, bruxism and other pathological etiologies [8,9]. Therefore, any neural interaction of the AT nerve can lead to a broad array of disorders such as neurologic, dystonic and neuromuscular disorders.…”

“…Examining the anatomy of the trigeminal nerve, we see connections to the CNS and its sensory branches that innervate most visceral structures such as the lung, the gastrointestinal tract, heart and immune cell rich tissues and organs such as spleen and lymph nodes. Therefore, TMD symptoms can be local and specific, and or varied and systemic such as: comorbid neurological conditions, including cervical dystonia, Parkinson's disease, Tourette syndrome, Blepharospasm and complex regional pain syndrome (CRPS) [8].…”

“…However, mounting evidence has shown that sustained systemic inflammation can initiate neurological diseases such as Alzheimer's disease and Parkinson's disease. The main cause is believed to be the hypersensitive state which microglia can enter upon continuous stimulation, which will result in excess production of proinflammatory mediators upon systemic inflammation, or injury [8]. Inflammation has been implicated in neuronal damage and cognitive impairment [12,13].…”