White matter brain and trigeminal nerve abnormalities in temporomandibular disorder

Massieh Moayedi, Irit Weissman-Fogel, Tim Vaughn Salomons, Adrian Philip Crawley, Michael Brian Goldberg, Bruce Victor Freeman, Howard Charles Tenenbaum, Karen Deborah Davis

Research output: Contribution to journalArticlepeer-review


Temporomandibular disorder (TMD) is a prevalent chronic pain disorder that remains poorly understood. Recent imaging studies reported functional and gray matter abnormalities in brain areas implicated in sensorimotor, modulatory, and cognitive function in TMD, but it is not known whether there are white matter (WM) abnormalities along the trigeminal nerve (CNV) or in the brain. Here, we used diffusion tensor imaging, and found that, compared to healthy controls, TMD patients had 1) lower fractional anisotropy (FA) in both CNVs; 2) a negative correlation between FA of the right CNV and pain duration; and 3) diffuse abnormalities in the microstructure of WM tracts related to sensory, motor, cognitive, and pain functions, with a highly significant focal abnormality in the corpus callosum. Using probabilistic tractography, we found that the corpus callosum in patients had a higher connection probability to the frontal pole, and a lower connection probability to the dorsolateral prefrontal cortex, compared to controls. Finally, we found that 1) FA in tracts adjacent to the ventrolateral prefrontal cortex and tracts coursing through the thalamus negatively correlated with pain intensity; 2) FA in the internal capsule negatively correlated with pain intensity and unpleasantness; and 3) decreases in brain FA were associated with increases in mean diffusivity and radial diffusivity, markers of inflammation and oedema. These data provide novel evidence for CNV microstructural abnormalities that may be caused by increased nociceptive activity, accompanied by abnormalities along central WM pathways in TMD.

Original languageEnglish
Pages (from-to)1467-1477
Number of pages11
Issue number7
StatePublished - Jul 2012
Externally publishedYes

Bibliographical note

Funding Information:
We thank Mr. Eugen Hlasny and Mr. Keith Ta for expert technical assistance, Dr. Yair Lenga for patient screening, Dr. Nathalie Erpelding and Ms. Danielle D. DeSouza for editing, and Drs. Stephen Smith, Heidi Johansen-Berg, and Thomas Nichols for their expert guidance and feedback on the analyses. This study was funded by: Canadian Institute of Health Research (CIHR) grant and funds from the Canada Research Chair program [MOP 53304] (to KDD); CIHR studentship (to MM); Ontario Graduate Scholarship (to MM); CIHR Strategic Training programs: Pain: Molecules to Community (to MM and IWF), and Cell Signals in Mucosal Inflammation and Pain [STP-53877] (to MM); University of Toronto Centre for the Study of Pain Clinician/Scientist Research fellowship (to IWF and TVS).


  • Chronic pain
  • DTI
  • MRI
  • Plasticity
  • TMD
  • Trigeminal nerve
  • White matter

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Anesthesiology and Pain Medicine


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