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Burning mouth syndrome (BMS) is a chronic intraoral pain syndrome. Previous studies have attempted to determine the brain connectivity features in BMS using functional and structural magnetic resonance imaging. However, no study has investigated the structural connectivity using multi-shell, multi-tissue-constrained spherical deconvolution (MSMT-CSD), anatomically constrained tractography (ACT), and spherical deconvolution informed filtering of tractograms (SIFT). Therefore, this study aimed to assess the differences in brain structural connectivity of patients with BMS and healthy controls using probabilistic tractography with these methods, and graph analysis. Fourteen patients with BMS and 11 age- and sex-matched healthy volunteers underwent 3-T magnetic resonance imaging. MSMT-CSD-based probabilistic structural connectivity was computed using the second-order integration over fiber orientation distributions algorithm based on nodes set in 84 anatomical cortical regions with ACT and SIFT. A t-test was performed for comparisons between the BMS and healthy control brain networks. The betweenness centrality was significantly higher in the left insula, right amygdala, and right lateral orbitofrontal cortex and significantly lower in the right inferotemporal cortex in the BMS group than that in healthy controls. However, no significant difference was found in the clustering coefficient, node degree, and small-worldness between the two groups. Graph analysis of brain probabilistic structural connectivity, based on diffusion imaging using an MSMT-CSD model with ACT and SIFT, revealed alterations in the regions comprising the pain matrix and medial pain ascending pathway. These results highlight the emotional-affective profile of BMS, which is a type of chronic pain syndrome.

The cause of burning mouth syndrome (BMS) is unknown. Although no effective treatment has been established, BMS patients frequently chew gum to alleviate pain. To identify the cause and new treatments for BMS, this study investigated the psychophysical and pharmacological properties of gum chewing to better understand its pain-relieving effects. In this prospective, blinded study, plasma catecholamine and serotonin levels and Profile of Mood States (POMS) scores were assessed after gum chewing or simulated chewing in 40 women (20 BMS patients and 20 age-matched controls). Visual analogue scale (VAS) scores for pain decreased significantly in BMS patients after gum chewing and simulated chewing. Moreover, resting VAS scores of BMS patients were significantly positively correlated with plasma adrenaline level. Furthermore, gum chewing was significantly correlated with lower plasma adrenaline level, VAS score, and tension-anxiety score. These results suggest that adrenaline is important in the pathogenesis of BMS pain and that the analgesic effect of gum chewing is induced through the potential effects of anxiety reduction, although this effect might not be specific to BMS. In addition, the analgesic effect of gum chewing was not induced solely by chewing motion.

Burning mouth syndrome (BMS) is classified into idiopathic orofacial pain conditions. Although central and peripheral neuropathic mechanisms are believed to be involved, the etiology remains to be fully elucidated. The present study examined temporal brain responses to an ongoing hot stimulus to investigate the pain modulating system in patients with BMS. The thermal stimulation sequence comprised baseline (32°C, 40 s) to warm (40°C, 32 s) to baseline (32°C, 40 s) to hot (49°C, 32 s), which was repeated four times using a Peltier thermode. These warm and hot stimuli were applied on the right palm and right lower lip in two separate sessions. Functional magnetic resonance imaging data were acquired by recording echo-planar images with a block design. Brain activity induced by purely hot stimulation (49°C vs. 40°C) applied to the palm was more pronounced than that induced by lip stimulation and in patients with BMS compared with controls. Comparison of brain activity between the first 16 s and second 16 s of the stimulus revealed pronounced time-dependent facilitation in patients with BMS during lip stimulation. These findings indicate that the pain modulating system in patients with BMS is dysregulated and that the brain in BMS is highly sensitized to pain information originating from the trigeminal system.

A standardized battery of quantitative sensory tests developed by the German Research Network on Neuropathic Pain (DFNS) was used to assess the association between somatosensory dysfunction and disease duration in patients with burning mouth syndrome (BMS). The 28 female participants with BMS were classified according to disease duration: ≤ 6 months (subchronic BMS, n = 15) and > 6 months (chronic BMS, n = 13); 29 age- and sex-matched healthy volunteers (control group) were recruited from staff of a dental hospital. The DFNS quantitative sensory testing protocol was applied at the ulnar surface of the right forearm and the tip of the tongue. Values for BMS patients and controls were compared and analyzed. The mechanical detection threshold (MDT) was significantly higher (i.e., loss of sensation) at the tongue tip in the chronic BMS group than in the control group (p = 0.011), whereas mechanical pain sensitivity (MPS) at the forearm was significantly higher (i.e., gain of sensation) in the chronic BMS group than in the control group (Z score = − 2.13 and 1.99, respectively). Multivariate analyses revealed that BMS patients could be discriminated from controls by using pressure pain threshold at the tongue (79.3%) (in the subchronic BMS group) and by MDT and MPS at the tongue tip and MPS at the forearm (96.6 and 89.7%, respectively) (in the chronic BMS group). In BMS patients with long disease duration, MDT showed loss of sensation. Increased MPS suggests that a neuropathic mechanism in the peripheral and central nervous systems is involved in BMS development.