Brain Signature of Chronic Orofacial Pain: A Systematic Review and Meta-Analysis on Neuroimaging Research of Trigeminal Neuropathic Pain and Temporomandibular Joint Disorders

Brain neuroimaging has been widely used to investigate the bran signature of chronic orofacial pain, including trigeminal neuropathic pain (TNP) and pain related to temporomandibular joint disorders (TMD). We here systematically reviewed the neuroimaging literature regarding the functional and structural changes in the brain of TNP and TMD pain patients, using a computerized search of journal articles via PubMed. Ten TNP studies and 14 TMD studies were reviewed. Study quality and risk of bias were assessed based on the criteria of patient selection, the history of medication, the use of standardized pain/psychological assessments, and the model and statistics of imaging analyses. Qualitative meta-analysis was performed by examining the brain regions which showed significant changes in either brain functions (including the blood-oxygen-level dependent signal, cerebral blood flow and the magnetic resonance spectroscopy signal) or brain structure (including gray matter and white matter anatomy). We hypothesized that the neuroimaging findings would display a common pattern as well as distinct patterns of brain signature in the disorders. This major hypothesis was supported by the following findings: (1) TNP and TMD patients showed consistent functional/structural changes in the thalamus and the primary somatosensory cortex, indicating the thalamocortical pathway as the major site of plasticity. (2) The TNP patients showed more alterations at the thalamocortical pathway, and the two disorders showed distinct patterns of thalamic and insular connectivity. Additionally, functional and structural changes were frequently reported in the prefrontal cortex and the basal ganglia, suggesting the role of cognitive modulation and reward processing in chronic orofacial pain. The findings highlight the potential for brain neuroimaging as an investigating tool for understanding chronic orofacial pain.