Structural connectivity changes in the cerebral pain matrix in burning mouth syndrome: a multi-shell, multi-tissue-constrained spherical deconvolution model analysis.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Salivary scintigraphy for Sjögren's syndrome in patients with xerostomia: A retrospective study.

OBJECTIVES: The value of salivary gland scintigraphy in the diagnosis of Sjögren's syndrome remains controversial. The primary aim of this study was to estimate the diagnostic accuracy of salivary gland scintigraphy in the diagnosis of Sjögren's syndrome among 237 patients with xerostomia. METHODS: We retrospectively compared eight scintigraphy parameters between 106 Sjögren patients and 131 non-Sjögren patients. RESULTS: Seven of the eight parameters were significantly decreased in patients with Sjögren; however, their diagnostic accuracy was low, with areas under the curves (AUCs) ranging from 0.58 (95% CI 0.50-0.65) to 0.63 (95% CI: 0.55-0.70). The prestimulatory oral activity index allowed discrimination between primary and secondary Sjögren's syndrome (AUC 0.73, 95% CI: 0.62-0.84), and the secretion velocity for parotid glands allowed discrimination between patients with Sjögren and burning mouth syndrome (AUC 0.71, 95% CI 0.59-0.82). CONCLUSION: The accuracy of scintigraphy parameters for the diagnosis of Sjögren's syndrome among patients with xerostomia was low; however, some functional indices appeared to assist discrimination between primary and secondary SS patients and between subgroups of patients with different causes of xerostomia.

Refractory burning mouth syndrome: clinical and paraclinical evaluation, comorbiities, treatment and outcome.

BACKGROUND: Burning Mouth Syndrome (BMS) is a chronic pain condition characterized by persistent intraoral burning without related objective findings and unknown etiology that affects elderly females mostly. There is no satisfactory treatment for BMS. We aimed to observe the long-term efficacy of high velanfaxine doses combined with systemic and topical administered clonazepam in a particular subgroup of BMS patients who do not respond to current clinical management. RESULTS: Eight (66.1 ± 6.2 years old females) out of 14 BMS patients fulfilled the inclusion criteria and were treated with venlafaxine (300 mg/d) and clonazepam (5 mg/d) for 35.4 ± 12.1 (mean ± SD) months. The average duration of the symptoms at baseline was 4.3 ± 1.4 years and the overall mean daily pain intensity score was 8.6 ± 1.3 (VAS); pain was in tongue and within the oral mucosa, accompanying by oral and facial dysesthesia. In five patients tasting was abnormal. All patients had positive history of concomitant primary headache. The average score of Hamilton Rating scale for Anxiety and Depression was 21 ± 4.2, and 26.1 ± 2.9, respectively. Previous ineffective treatments include anticonvulsants and anti-depressants. All patients responded (more than 50% decrease in VAS) after three months treatment (mean VAS 3.2 ± 2.2) with no remarkable adverse events. CONCLUSION: BMS deserves bottomless psychiatric evaluation and management when current available treatments fail. Treatment with venlafaxine combined with topical and systemic clonazepam may be effective in refractory BMS cases but further investigation in a large-scale controlled study is needed to confirm these results.

Grey matter changes of the pain matrix in patients with burning mouth syndrome.

Burning mouth syndrome (BMS) is characterized by a burning sensation in the mouth, usually in the absence of clinical and laboratory findings. Latest findings indicate that BMS could result from neuropathic trigeminal conditions. While many investigations have focused on the periphery, very few have examined possible central dysfunctions. To highlight changes of the central system of subjects with BMS, we analysed the grey matter concentration in 12 subjects using voxel-based morphometry. Data were compared with a control group (Ct). To better understand the brain mechanisms underlying BMS, the grey matter concentration of patients was also compared with those of dysgeusic patients (Dys). Dysgeusia is another oral dysfunction condition, characterized by a distorted sense of taste and accompanied by a reduced taste function. We found that a major part of the 'pain matrix' presented modifications of the grey matter concentration in subjects with BMS. Six regions out of eight were affected [anterior and posterior cingulate gyrus, lobules of the cerebellum, insula/frontal operculum, inferior temporal area, primary motor cortex, dorsolateral pre-frontal cortex (DLPFC)]. In the anterior cingulate gyrus, the lobules of the cerebellum, the inferior temporal lobe and the DLPFC, pain intensity correlated with grey matter concentration. Dys also presented changes in grey matter concentration but in different areas of the brain. Our results suggest that a deficiency in the control of pain could in part be a cause of BMS and that BMS and dysgeusia conditions are not linked to similar structural changes in the brain.

Low regional cerebral blood flow in burning mouth syndrome patients with depression.

OBJECTIVES: The main aims of this study were to (i) investigate the emotional disorder status of patients with burning mouth syndrome (BMS) and (ii) detect regional cerebral blood flow in BMS patients with the application of combined single-photon emission computed tomography and computed tomography (SPECT/CT). SUBJECTS AND METHODS: The degree of pain was measured using the visual analysis scale, and emotional disorder with the self-rating anxiety scale, self-rating depression scale, and Hamilton depression rating scale in 29 patients with BMS and 10 healthy controls. SPECT/CT was performed in 29 patients with BMS and 10 healthy controls, and statistical parametric mapping method was used for between-group analyses. RESULTS: The incidence rate of depression in patients with BMS was 31.0%. Compared to the control group, patients with BMS displayed significantly different depression and anxiety scales (P < 0.05). Significantly lower regional cerebral blood flow in the left parietal and left temporal lobes was recorded for BMS patients with depression (P < 0.05). CONCLUSIONS: Patients with BMS experience more depression and anxious emotion. Moreover, depression in patients with BMS may be associated with lower regional cerebral blood flow in the left temporal and left parietal lobes.

White and Gray Matter Abnormality in Burning Mouth Syndrome Evaluated with Diffusion Tensor Imaging and Neurite Orientation Dispersion and Density Imaging.

PURPOSE: Burning mouth syndrome (BMS) is defined by a burning sensation or pain in the tongue or other oral sites despite the presence of normal mucosa on inspection. Both psychiatric and neuroimaging investigations have examined BMS; however, there have been no analyses using the neurite orientation dispersion and density imaging (NODDI) model, which provides detailed information of intra- and extracellular microstructures. Therefore, we performed voxel-wise analyses using both NODDI and diffusion tensor imaging (DTI) models and compared the results to better comprehend the pathology of BMS. METHODS: Fourteen patients with BMS and 11 age- and sex-matched healthy control subjects were prospectively scanned using a 3T-MRI machine using 2-shell diffusion imaging. Diffusion tensor metrics (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity [AD], and radial diffusivity [RD]) and neurite orientation and dispersion index metrics (intracellular volume fraction [ICVF], isotropic volume fraction [ISO], and orientation dispersion index [ODI]) were retrieved from diffusion MRI data. These data were analyzed using tract-based spatial statistics (TBSS) and gray matter-based spatial statistics (GBSS). RESULTS: TBSS analysis showed that patients with BMS had significantly higher FA and ICVF and lower MD and RD than the healthy control subjects (family-wise error [FWE] corrected P < 0.05). Changes in ICVF, MD, and RD were observed in widespread white matter areas. Fairly small areas with different FA were included. GBSS analysis showed that patients with BMS had significantly higher ISO and lower MD and RD than the healthy control subjects (FWE-corrected P < 0.05), mainly limited to the amygdala. CONCLUSION: The increased ICVF in the BMS group may represent myelination and/or astrocytic hypertrophy, and microstructural changes in the amygdala in GBSS analysis indicate the emotional-affective profile of BMS.

Striatal dopamine D1 and D2 receptors in burning mouth syndrome.

Animal studies have indicated that the nigrostriatal dopaminergic system is involved in central pain modulation. In a recent positron emission tomography (PET) study, we demonstrated presynaptic dysfunction of the nigrostriatal dopaminergic pathway in burning mouth syndrome, which is a chronic pain state. The objective of the present study was to examine striatal dopamine D1 and D2 receptors in these patients. We used 11C-NNC 756 and 11C-raclopride to study D1 and D2 receptor binding in a PET study in ten burning mouth patients and 11 healthy controls. Patients underwent a structured psychiatric evaluation and an electrophysiological test for the excitability of the blink reflex. The striatal uptake of 11C-NNC 756 did not differ between patients and controls. In a voxel-level analysis, the uptake of 11C-raclopride was statistically significantly higher in the left putamen in burning mouth patients (corrected P-value 0.038 at cluster-level). In the region of interest analysis, the D1/D2 ratio was 7.7% lower in the right putamen (0.64+/-0.04 vs. 0.69+/-0.04, P=0.01) and 6.4 % lower in the left putamen (0.65+/-0.05 vs. 0.70+/-0.05, P=0.05) when compared to controls. Increased 11C-raclopride uptake and the subsequent decrease in the D1/D2 ratio may indicate a decline in endogenous dopamine levels in the putamen in burning mouth patients.

Role of the dopaminergic system in chronic pain -- a fluorodopa-PET study.

Recent data from animal experiments suggest an important role for the basal ganglia in the processing and sensorimotor gating of nociceptive information. However, very little is known about their possible participation in human pain. Because of our previous finding of increased excitability of the blink reflex (a brainstem reflex under dopaminergic inhibitory control) in some burning mouth syndrome (BMS) patients, we have studied the dopaminergic function of the striatum (putamen and caudatus) of BMS patients with positron emission tomography (PET). 6-[(18)F]fluorodopa (FDOPA) PET scans were done on ten BMS patients and 14 healthy control subjects. The presynaptic dopaminergic function was significantly decreased in the right putamen (20%, P=0.04) of the BMS patients compared to control subjects. On the left side, the FDOPA uptake was decreased by 17% (P=0.08). The mean FDOPA uptake was not significantly changed in the caudate nucleus of the patients. The finding of decreased striatal FDOPA uptake in the putamen supports our previous neurophysiological observations indicating decreased dopaminergic inhibition in BMS patients. The present result provides direct evidence of the involvement of the nigrostriatal dopaminergic system in pain for the first time in a clinical pain condition.