Burning Mouth Syndrome Patients Research Articles

Proteomic profiling of whole-saliva reveals correlation between Burning Mouth Syndrome and the neurotrophin signaling pathway

Burning mouth syndrome (BMS) is characterized by a spontaneous and chronic sensation of burning in the oral mucosa, with no apparent signs. The underlying pathophysiological and neuropathic mechanisms remain unclear. Here, we attempt to elucidate some of these mechanisms using proteomic profiling and bioinformatic analyses of whole-saliva (WS) from BMS patients compared to WS from healthy individuals. Qualitative and quantitative proteomic profiling was performed using two dimensional gel electrophoresis (2-DE) and quantitative mass spectrometry (q-MS). In order to improve protein visibility, 21 high abundance proteins were depleted before proteomic profiling. Quantitative proteomic analysis revealed 100 BMS specific proteins and an additional 158 proteins up-regulated by more than threefold in those with BMS. Bioinformatic analyses of the altered protein expression profile of BMS group indicated high correlations to three cellular mechanisms including the neurotrophin signaling pathway. Based on this finding, we suggest that neurotrophin signaling pathway is involved in the pathophysiology of BMS by amplifying P75NTR activity, which in turn increases neural apoptosis thereby reducing sub-papillary nerve fiber density in the oral mucosa.

Neurophysiology and genetics of burning mouth syndrome.

Neuropathic mechanisms are involved in burning mouth syndrome (BMS), and variation of the dopamine D2 receptor (DRD2) gene contributes to experimental pain perception. We investigated whether neurophysiologic findings differ in BMS patients compared to healthy controls, and whether 957C>T polymorphism of the DRD2 gene influences thermal sensitivity or pain experience in BMS. Forty-five BMS patients (43 women), mean age 62.5years, and 32 healthy controls (30 women), mean age 64.8years, participated. Patients estimated pain intensity, interference, suffering and sleep with Numeric Rating Scale. Blink reflex tests of the supraorbital (SON), mental (MN) and lingual (LN) nerves, and thermal quantitative sensory testing were done. The results were analysed with ANOVA. DRD2 gene 957C>T polymorphism was determined in 31 patients, and its effects on neurophysiologic and clinical variables were analysed. Cool (p=0.0090) and warm detection thresholds (p=0.0229) of the tongue were higher in BMS patients than controls. The stimulation threshold for SON BR was higher in patients than in controls (p=0.0056). The latencies of R2 component were longer in BMS patients than in controls (p=0.0005) at the SON distribution. Habituation of SON BR did not differ between the groups. The heat pain thresholds were highest (p=0.0312) in homozygous patients with 957TT, who also reported most interference (p=0.0352) and greatest suffering (p=0.0341). Genotype 957CC associated with sleep disturbances (p=0.0254). Burning mouth syndrome patients showed thermal hypoesthesia within LN distribution compatible with small fibre neuropathy. The DRD2 957C>T genotype influences perception and experience of BMS pain. The results confirm earlier findings of neuropathic pain in BMS. The DRD2 957 C>T genotype influences perception and experience of clinical pain in BMS.

Change in gray matter volume and cerebral blood flow in patients with burning mouth syndrome.

The purpose of this study was to evaluate alterations in gray matter volume (GMV) and cerebral blood flow (CBF) using structural MRI and arterial spin labeling (ASL) perfusion MRI, respectively, in burning mouth syndrome (BMS) patients METHODS: We prospectively enrolled 12 patients with BMS and 14 healthy controls. Volumetric T1-weighted magnetization-prepared rapid gradient-echo imaging and pseudo-continuous ASL were performed to obtain GMV and CBF, respectively. We analyzed differences in the GMV and CBF between the two groups, and their correlations with clinical parameters. The GMV was smaller in the left thalamus and left middle temporal gyrus in the BMS group when compared to controls. Regional CBF in the BMS group was significantly decreased in the left middle temporal gyrus, left insula, right middle temporal gyrus, and right insula compared with controls. In BMS patients, there was a significant correlation between GMV and pain severity in the left middle temporal gyrus. The reduced GMV seen in the thalami of BMS patients is consistent with the pattern observed in those with chronic pain disease, which implies that the pathogenesis of BMS may be associated with atrophy of the brain structures associated with thalamocortical processing. In addition, changes in CBF in the insula and middle temporal gyrus were also observed.

Quantified Magnetic Resonance Spectroscopy in the Diagnosis of Burning Mouth Syndrome

Purpose: To investigate potential pathological differences in major brain metabolites in burning mouth syndrome (BMS). Materials and Methods: We prospectively evaluated eight patients and six healthy controls with single voxel magnetic resonance (MR) spectroscopy throughout 2017 using 3-Tesla MR unit. Metabolite levels measured from the left posterior paracingulate white matter. Raw images were processed with Tarquin version 4.3.10 and area under curve values were automatically calculated for GABA (γ-Aminobutyric acid), Ins (myo-inositole), tNAA (N-Acetylaspartate), tCho (total choline), tCr (total creatine) and GLx (glutamine + Glutamat). Major metabolite levels and all metabolites ratio to tCr calculated and compared between two groups using Mann-Whitney U test. Results: GABA/tCR value of the patients (0.589 ± 0.194, median = 0.515) was significantly higher than control group (0.230 ± 0.067, median = 0.220) (P = 0.002). tNAA/tCR value of the patients (1.106 ± 0.218, median: 1.205), was significantly lower than the control group (1.538 ± 0.401, median: 1.705) (P = 0.028). No significant difference was observed between two groups in terms of all other metabolites (P > 0.05). Conclusion: We demonstrated increased GABA and decreased NAA in the left posterior paracingulate region in BMS patients. We suggest that these metabolite alterations in central nervous system might play a key role in the etiology of the disease by inhibiting the suppression of burning sensation.

Evaluation of the effectiveness of crocin isolated from saffron in treatment of burning mouth syndrome: A randomized controlled trial.

Objective:Burning mouth syndrome (BMS) is a debilitating disorder with few limited treatment modalities. Because of the proven association between BMS symptoms, and depression and anxiety, treatment modalities that alleviate the two latter etiologic factors can be clinically effective. Thus, owing to the antidepressant and potential analgesic effects of crocin (as an active constituent of saffron), the present study was performed to compare the effect of crocin and citalopram (as control) on BMS symptoms and depression/anxiety in patients with BMS. Materials and Methods:The present double-blind randomized clinical trial was carried out on BMS patients. Patients were randomly divided into citalopram (n=21) and crocin (n=26) groups and treated for 11 weeks. BMS symptoms (based on Visual Analysis Scale (VAS)), as well as anxiety and depression (based on Hamilton questionnaire) were evaluated at baseline and during the treatment period. Mann-Whitney, Chi-Square test, Independent t-test, Friedman, and Spearman correlation were employed for statistical analysis.Results:Our findings showed a significant effect for crocin on the severity of BMS symptoms, anxiety and depression in BMS patients. Conclusion:Crocin can be considered for treatment of BMS subjects with concurrent anxiety and/or depression.

Low-level laser therapy in patients with Burning Mouth Syndrome: A double-blind, randomized, controlled clinical trial.

BackgroundEvaluate the effect of LLLT in the treatment of burning mouth syndrome (BMS).Material and MethodsTwenty-one BMS patients were randomly assigned to two groups: 12 in the laser group (LG) and 9 in the control group (CG). Patients in the LG underwent 2-week sessions of LLLT for 4 weeks. The spot tip area of this tool is 0.088cm2, semi-conductor GaAlAs, with a wavelength of 808nm ±5nm (infrared), 200 mW output power, 1.97W/cm2 of power density, 3 J energy per point and application time 15 seconds per point. LLLT was applied punctually, in continuous emissions, on each of the sites where there was a symptom. Symptoms were evaluated with a visual analogue scale (VAS) and patient psychological profiles were assessed using the Hospital Anxiety-Depression Scale. No side effects were recorded. Statistical analysis was carried out via ANOVA and logistic regression analysis.ResultsThe initial VAS score mean was 8.9 for the LG and 8.3 for the CG (p >0.05). After the eighth session the VAS score was 5.5 and 5.8 respectively, and at two months it was 4.7 and 5.1 respectively. Improvement variables were established by dichotomizing the pain scales. We obtained levels of significance for the improvement variable for the LG at the two-month follow-up (p=0.0038) and for the univariate analysis of the treatment. The improvement was marginally significant in the multivariant analysis of: dry mouth, dysgeusia, pain and the treatment (p=0.0538).ConclusionsLLLT may be an alternative treatment for the relief of oral burning in patients with BMS. Key words:Burning mouth syndrome, oral pain, laser dentistry, laser therapy, low intensity laser therapy.

Association of somatosensory dysfunction with symptom duration in burning mouth syndrome.

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: ≤ 6months (subchronic BMS, n = 15) and > 6months (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.

Psychological problems and quality of life of patients with oral mucosal diseases: a preliminary study in Chinese population

BackgroundPsychological problems might play important roles in oral mucosal diseases such as recurrent aphthous ulcers (RAU), oral lichen planus (OLP), burning mouth syndrome (BMS), but the relevance to patients’ quality of life remained controversial. The aim of this study was to investigate the psychological problems and oral health-related quality of life in patients with RAU, OLP, and BMS in China, to assess the relationship between psychological problems and quality of life.MethodThirty-nine RAU patients, 45 OLP patients, 15 BMS patients and 45 healthy controls were enrolled in the study. Hospital Anxiety and Depression Scale (HADS) were chosen to analyze the patients’ psychological problems. Oral Health Impact Profile (OHIP-14) was used to measure the OHRQoL. The scores of HADS and OHIP-14 were used to analyze the relationship between psychological problems and the quality of life of oral mucosa patients.ResultsEach of OHIP-14 scores and HADS scores in RAU, OLP, BMS was higher than the control group, and there was significant difference in the patients groups with the control cases(P < 0.05). OHIP-14 score of RAU was the highest in three patient groups. Its OHRQoL was lowest in the three groups, which had statistical significance (P < 0.05). Positive correlations existed between the psychological problems and the quality of life of the three patient groups (rs > 0, P < 0.05), except for the depression of the BMS group (rs = 0.168, P = 0.395).ConclusionPatients with oral mucosal diseases such as RAU, OLP, and BMS had higher levels of anxiety, depression, and lower quality of life. The patient’s psychological problems were related to their quality of life, suggesting that the psychological state of patients with oral mucosal disease need more attention.

Proteomics of the acid-soluble fraction of whole and major gland saliva in burning mouth syndrome patients

ObjectiveIn the present study the salivary proteome of burning mouth syndrome patients and healthy subjects was characterized by a top-down proteomic approach and compared to highlight possible qualitative and quantitative differences that may give suggestions about the causes of this pathology which are still unknown. Materials and methodsResting and stimulated whole saliva, stimulated parotid and submandibular/sublingual saliva samples were collected from burning mouth syndrome patients (n = 16) and age- and gender-matched healthy subjects (n = 14). An equal volume of 0.2% trifluoroacetic acid was added to each sample immediately after collection and the supernatants were analysed by liquid chromatography coupled to electrospray-ionisation mass spectrometry. Proteins and peptides were quantified using a label-free approach measuring the extracted ion current peak areas of the main salivary proteins and peptides. ResultsThe quantitation of the main salivary proteins and peptides revealed a higher concentration of cystatin SN in resting saliva of burning mouth syndrome patients with respect to healthy controls and no other conspicuous changes. ConclusionsThe reported data showed that the salivary protein profile was not affected, in composition and relative abundance, by the burning mouth syndrome, except for the cystatin SN, a protein up-regulated in several pathological conditions, that might be considered potentially indicative of the disease.

Burning mouth syndrome in postmenopausal women with self-reported sleep problems

ABSTRACT Objective The aim of this study was to investigate possible relationships among hematologic factors, psychological dimensions, the presence of self-reported sleep problems, and clinical characteristics in patients with burning mouth syndrome (BMS). Methods Twenty-five postmenopausal female patients with primary BMS (aged 55.2 ± 9.6 years) were included. All participants underwent clinical and psychological evaluations and blood sampling. The patients were subdivided according to the absence or presence of the self-reported sleep problems. Results Pain intensity of BMS patients with sleep problems was significantly higher than those without sleep problems, and the severity of oral complaints was correlated with the presence of depression, anxiety, hostility, phobia, and psychosis. Estradiol levels were significantly lower, and FSH and LH levels were higher in BMS patients with sleep problems than those without sleep problems. Discussion BMS patients with sleep problems may suffer inharmonious psychoneuroendocrinological interactions that might worsen oral BMS symptoms.

An increase in corrected QT interval may indicate a good clinical response to amitriptyline in female patients with burning mouth syndrome

Burning mouth syndrome (BMS) is characterized by a burning sensation of the oral mucosa in the absence of underlying causes. BMS patients can pose a therapeutic challenge to clinicians. Amitriptyline has been a first-line treatment for BMS and is known to prolong corrected QT interval (QTc) in a dose dependent manner. However, little is known about the QTc lengthening effect of amitriptyline at analgesic dosages. The objective of this study was to evaluate changes in QTc in female BMS patients treated with amitriptyline. We conducted a single-center retrospective observational study and evaluated 40 female BMS patients. The QTc interval did not show statistically significant increase with amitriptyline (p=0.1502). However, the change in QTc of amitriptyline-responders was significantly longer than that of nonresponders (p=0.0142). The change in QTc may be a non-invasive maker of clinical responses to amitriptyline in female BMS patients.

Mechanical sensitivity and psychological factors in patients with burning mouth syndrome.

The aim of this study was to compare mechanical sensitivity on the tongue using quantitative sensory testing (QST) and psychological factors using the General Health Questionnaire (GHQ) between burning mouth syndrome (BMS) patients and healthy participants. Participants comprised 20 female BMS patients (68.1 ± 7.4years) and 20 healthy females (65.4 ± 4.6years). Psychological factors were evaluated with GHQ. Tactile detection thresholds (TDT) and filament-prick pain detection thresholds (FPT) were used to evaluate mechanical sensitivity on the tongue in all participants. TDT and FPT were measured on the tongue within both the painful area and the non-painful area in BMS patients, and on the tongue on both sides in healthy participants. As controls, TDT and FPT were measured with Semmes-Weinstein monofilaments on the skin of the mentum and palm in all participants. GHQ scores were significantly higher in BMS patients than in healthy participants (P = 0.024). No significant differences in TDT or FPT on the tongue, mentum, or palm were seen between BMS patients and healthy participants (P > 0.05). BMS patients showed no significant differences in TDT or FPT between the painful and non-painful areas on the tongue (P > 0.05). There were no significant correlations among TDT/FPT and GHQ score in BMS patients (P > 0.05). These findings could indicate a more important role for psychological factors than mechanical sensitivity in BMS pathophysiology. Pain on the tongue in elderly female patients with BMS may be more related to psychological factors.

Melatonin Treatment in Patients with Burning Mouth Syndrome: A Triple-Blind, Placebo-Controlled, Crossover Randomized Clinical Trial.

To evaluate the efficacy of melatonin compared to placebo in reducing pain associated with burning mouth syndrome (BMS), as well as side effects of treatment and effects on sleep quality, anxiety, and serum and salivary melatonin levels. In this triple-blind, randomized clinical trial, 20 BMS patients (mean age ± standard deviation: 64.4 ± 11.5 years; range: 35 to 82 years) were enrolled to receive melatonin (12 mg/day) or placebo for 8 weeks in a crossover design. After treatment, changes in pain from baseline were ascertained by patient self-assessment with a verbal category scale and a visual analog scale. Secondary outcomes included evaluation of changes in sleep quality and anxiety. Data were subjected to analysis of variance (ANOVA), Fisher exact test, paired t test, Wilcoxon signed rank test, or chi-square test, as appropriate. Melatonin was not superior to placebo in reducing pain. Melatonin significantly improved anxiety scores, though without strong clinical relevance. Independent of treatment, sleep quality did not significantly change during the trial, although melatonin slightly increased the number of hours slept. After active treatment, the mean ± standard error serum melatonin level peaked at 1,520 ± 646 pg/mL. A generally safe pharmacologic profile of melatonin was observed, and the placebo and melatonin treatments resulted in similar adverse effects. Within the limitations of this study, melatonin did not exhibit higher efficacy than placebo in relieving pain in BMS patients.

Burning mouth syndrome in Iraqi patients: a preliminary study of 38 cases.

The complain of burning sensation in the mouth can be said to be a symptom of other disease or a syndrome in its own right of unknown etiology. In patients where no underlying dental or medical causes are identified and no oral signs are found, the term burning mouth syndrome should be used.To obtain base line information on the prevalence of the oral problems and clinical features co-existing with burning mouth syndrome patients.The study group consisted of 38 (11 males and 27 females) burning mouth patients, they were examined to evaluate the oral health status.Of 38 patients, who verbalized their complaints, 63.1% complained of subjective oral dryness, 26.3% had taste disturbances; the most prevalent site with burning sensations was the tongue 65.7%.Burning mouth syndrome patients in our environment are principally women, other symptoms include dryness and altered taste is common in those patients.

Burning mouth syndrome in Iraqi patients: a preliminary study of 38 cases

The complain of burning sensation in the mouth can be said to be a symptom of other disease or a syndrome in its own right of unknown etiology. In patients where no underlying dental or medical causes are identified and no oral signs are found, the term burning mouth syndrome should be used.To obtain base line information on the prevalence of the oral problems and clinical features co-existing with burning mouth syndrome patients.The study group consisted of 38 (11 males and 27 females) burning mouth patients, they were examined to evaluate the oral health status.Of 38 patients, who verbalized their complaints, 63.1% complained of subjective oral dryness, 26.3% had taste disturbances; the most prevalent site with burning sensations was the tongue 65.7%.Burning mouth syndrome patients in our environment are principally women, other symptoms include dryness and altered taste is common in those patients.

The association between burning mouth syndrome and sleep disturbance: A case-control multicentre study.

To investigate the quality of sleep and the psychological profiles of a large cohort of Italian patients with burning mouth syndrome (BMS) and to clarify the relationships between these variables and pain. In this case-control study, 200 patients with BMS vs an equal number of age- and sex-matched healthy controls, recruited in 10 universities, were enrolled. The Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), Numeric Pain Intensity Scale (NRS) and Total Pain Rating Index (T-PRI) were administered. Descriptive statistics, including the Mann-Whitney U test and hierarchical multiple linear regression analysis, were used. Poor sleep quality (PSQI≥5) was present in 78.8% (160) patients with BMS. BMS patients had statistically higher scores in all items of the PSQI and ESS than the healthy controls (p<.001). A depressed mood and anxiety correlated positively with sleep disturbance. The Pearson correlations were 0.570 for the PSQI vs HAM-D (p<.001) and 0.549 for the PSQI vs HAM-A (p<.001). Pain intensity (NRS) poorly correlated to sleep quality; the Pearson correlation was 0.162 for the PSQI vs NRS (p=.021). The BMS patients showed a poor sleep quality, anxiety and depression, as compared with the controls, highlighting the relationships between oral burning, sleep and mood.

Comparison between burning mouth syndrome patients with and without psychological problems

The purpose of this study was to compare clinical and socio-demographic characteristics between burning mouth syndrome (BMS) patients with and without psychological problems. Of 644 patients with symptoms of oral burning, 224 with primary BMS were selected on the basis of laboratory testing, medical history, and psychometric tests: 39 with psychological problems (age 62.5±11.5years) and 185 without psychological problems (age 58.4±11.4years). Comprehensive clinical and socio-demographic characteristics, including psychological profiles and salivary flow rates, were compared between the two groups. No significant difference in sex ratio, duration and diurnal pattern of symptoms, unstimulated whole saliva flow rate, or marital status was found between the groups. The patients with psychological problems had a significantly higher mean age, reduced stimulated whole saliva flow rate, and lower level of education than those without psychological problems. The patients with psychological problems also displayed higher rates and greater severity of various types of BMS-related symptom in most parts of the oral mucosa, higher rates of stress-related symptoms, and greater difficulties in daily activities. The severity of taste disturbance was the factor most significantly correlated with the level of psychometry. In conclusion, psychological problems in BMS patients are associated with an aggravation of BMS symptoms.

Plasma N-acylethanolamine and endocannabinoid levels in burning mouth syndrome: Potential role in disease pathogenesis.

The objective was to measure endocannabinoid (eCB) ligands and non-cannabinoid N-acylethanolamine (NAE) molecules in plasma from individuals with burning mouth syndrome (BMS) and to determine whether plasma eCB/NAE levels correlated with pain, inflammation and depressive symptomatology in this cohort. Plasma content of the eCBs, anandamide (AEA) and 2-arachidonoyl-glycerol (2-AG), and the NAE molecules, palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) were assessed in healthy subjects (n = 8) and in a cohort of newly diagnosed BMS patients (n = 9) using liquid chromatography-tandem mass spectrometry. Plasma eCBs and NAE profiles were correlated with self-rated oral cavity pain intensities, depressive symptomatology and plasma IL-8 levels. Plasma levels of PEA, but not OEA, AEA or 2-AG, were significantly elevated in patients with BMS, when compared to plasma from healthy individuals. Plasma PEA, OEA and AEA levels correlated with depressive symptomatology. This is the first evidence to indicate that circulating eCB/NAE levels are altered in BMS.

Understanding of Burning Mouth Syndrome Based on Psychological Aspects.

Burning mouth syndrome (BMS) is a chronic pain condition characterised by a persistent burning sensation in clinically normal oral mucosa. BMS most commonly occurs in middleaged and elderly women. Various local and systemic factors can cause oral burning symptoms. When all possible local and systemic factors are excluded, burning mouth symptoms can be diagnosed as BMS. Psychophysical tests and histopathological data suggest the involvement of peripheral and central neuropathic mechanisms in BMS etiopathogenesis. Psychological problems are frequently observed in BMS patients. Several mechanisms, including increased parafunctional habits, steroid dysregulation, central disinhibition due to taste dysfunction, and low dopamine levels in the brain, have been proposed as an explanation for the role of psychological factors in BMS pathophysiology. However, the causal relationship between BMS and psychological problems remains controversial. Given the neuropathic nature of BMS, treatment for it is similar to other neuropathic pain conditions. Although various treatment modalities, including pharmacological intervention, behavioural therapy and psychotherapy, have been proposed, there is no definitive treatment always effective for the majority of BMS patients. In conclusion, for better understanding of the relationship between BMS and psychological factors, well-designed prospective studies are needed. In addition, the evaluation and treatment of psychological problems are essential for successful management of BMS patients.

Burning Mouth Syndrome: Patient Profiles, Clinical Symptoms, Affecting Associated Factors, and Treatment Responses

Background: The clinical characteristics of burning mouth syndrome (BMS) are not fully understood. We investigated the profiles of BMS patients, characteristics associated with BMS, and the available treatment methods and their effects. Methods: Seventy-four BMS patients without oral mucosal lesions were enrolled. Their medical history, medications taken, and symptom scores were investigated via questionnaires. Laboratory investigations of parameters potentially associated with BMS were performed. Regarding treatment, 0.01% dexamethasone gargle, amitriptyline, and clonazepam were administered individually or in combination, depending on the degree of symptom improvement. Symptoms were scored from 0 - 10 points; these scores were used to evaluate treatment efficacy and patient satisfaction. Results: Mean age of the patients was 63.6 ± 14.2 years; mean symptom prevalence period was 15.5 ± 24.7 months. BMS was not significantly associated with a history of hypertension, diabetes, or any specific medications. Treatment reduced the symptoms of 85.1% subjects (63/74). Conclusions: Contrary to that in previous studies, we observed significant improvements in BMS patients following combination treatment with dexamethasone gargle, amitriptyline, and clonazepam.