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

Abstract

Background: The temporomandibular joint (TMJ) is well innervated by braches of the trigeminal nerve. The temporomandibular joint disorders (TMD) can cause neural-inflammation in the peripheral nervous system (PNS) at the site of injury, or compression, and may have systemic effects on the central nervous system (CNS). Neural-inflammation causes elevations in cytokine expression and microglia activation. When the site of injury, or compression is treated, or relieved, neural inflammation is reduced. These changes can be seen and measured with fMRI brain activities.

Methods: For this study, patients with comorbid TMD and systemic/neurologic conditions were compared using clinical diagnostic markers, inflammatory, pain, tissue destruction enzymatic biomarkers, and functional magnetic resonance imaging (fMRI) activity of the brain, with and without a custom-made dental orthotic.

Results: Our results showed a correlation between the clinical diagnosis of the pathological TMJ, biomarkers and the fMRI study. There was a marked elevation of biomarkers in samples taken from TMJ of patients who were clinically diagnosed with TMD. The fMRI study of TMD patients showed an abnormal hyper-connected salience network and a diminished blood flow to the anterior frontal lobes when they did not wear their customized dental orthotics.

Conclusions: Our findings highlight the importance of TMJ-CNS connections and use of fMRI as an investigative tool for understanding TMD and its related neurological pathologies.

Keywords: Arterial spin labeling (ASL); Blood oxygenation level dependent (BOLD); Default mode network (DMN); Dental orthotic; Fractional anisotropy (FA); Functional magnetic resonance imaging (fMRI); Microglia cells; Temporomandibular joint (TMJ); Temporomandibular joint disorders (TMD); Trigeminal ganglion (TG).

Fig. 1

a Pre-treatment anterior/posterior cephalometric, b pre-treatment lateral cephalometric, c sagittal view right and left TMJ, d anteroposterior view of right and left TMJ, notice the Bifid shape of the right TMJ, e panographic film shows the joint position with the splint in the mouth, f frontal view with the splint in the mouth, g lateral view with the dental orthotic in the mouth, h joint vibration analysis indicating left TMJ disc displacement with reduction

Fig. 2

a Salient network analysis of patient 9 without and with dental orthotic, b default Mode Network analysis of patient 9 without and with dental orthotic, c arterial spin labeling analysis of patient 9 without and with dental orthotic

Fig. 2

a Salient network analysis of patient 9 without and with dental orthotic, b default Mode Network analysis of patient 9 without and with dental orthotic, c arterial spin labeling analysis of patient 9 without and with dental orthotic

Fig. 3

a Frontal cephalometric before treatment, demonstrating the head position. b lateral cephalometric before treatment, c right and Left tomography before treatment, d lateral cephalometric demonstrating dental orthotic in the mouth, e frontal View, notice the head is more leveled with the dental orthotic, f Tomography of the Right and Left TMJ showing condylar position with the dental orthotic in the mouth. g EMG pre-treatment, notice the high activity of the right SCM at 286 micro-volts. h EMG with splint in, notice the decrease in activity of the SCM muscles. The temporalis and right masseter are slightly elevated and the patient is gently clenching on the dental orthotic

Fig. 4

a Salient network analysis of patient 10 without and with dental orthotic, b default mode network analysis of patient 10 without and with dental orthotic, c arterial Spin Labeling analysis of patient 10 without and with dental orthotic

Fig. 4

a Salient network analysis of patient 10 without and with dental orthotic, b default mode network analysis of patient 10 without and with dental orthotic, c arterial Spin Labeling analysis of patient 10 without and with dental orthotic

Fig. 5

a Panoramic, b AP cephalometric, c lateral cephalometric, d right and left TMJ tomography

Fig. 6

a Salient network analysis of patient 11 without and with dental orthotic, b default mode network analysis of patient 11 without dental orthotic volume 1 and 2, c default mode network analysis of patient 11 with dental orthotic volume 1 and 2, d arterial spin labeling analysis of patient 11 without and with dental orthotic

Fig. 6

a Salient network analysis of patient 11 without and with dental orthotic, b default mode network analysis of patient 11 without dental orthotic volume 1 and 2, c default mode network analysis of patient 11 with dental orthotic volume 1 and 2, d arterial spin labeling analysis of patient 11 without and with dental orthotic