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

BACKGROUND: 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. RESULTS: 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. CONCLUSION: 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.

Plasma IL-8 signature correlates with pain and depressive symptomatology in patients with burning mouth syndrome: Results from a pilot study.

BACKGROUND: Burning mouth syndrome (BMS) is a neuropathic orofacial pain condition of unknown aetiology that encompasses intra-oral burning pain without abnormal clinical findings. Psychological, neural and inflammatory processes are associated with BMS pathogenesis. Currently, studies characterising plasma cytokine/chemokine profiles with pain and depression in patients with BMS are lacking. Considering that inflammation is associated with the pathophysiology of BMS, and that inflammation is closely associated with pain and depression, we aimed to correlate depressive symptomatology and oral cavity pain with plasma cytokine/chemokine signatures in a cohort of patients with BMS. METHODS: In this study, plasma protein levels of Th1 cytokines (IFN-γ, IL-2, IL-12p70, TNF-α), Th2 cytokines (IL-4, IL-10, IL-6, IL-13) and the chemokine IL-8 were assessed in patients with BMS (n = 10) and healthy volunteers (n = 10), using pro-inflammatory-10-plex assays. Clinical histories, alongside self-rated oral cavity pain intensities and depressive symptomatology were assessed using a visual analogue scale and the 16-item Quick Inventory of Depressive Symptomatology questionnaires, respectively. RESULTS: We present evidence that BMS is associated with increased depressive symptomatology and enhanced oral cavity pain. Plasma isolated from BMS patients display enhanced expression of the pro-inflammatory chemokine IL-8, when compared to plasma from healthy individuals. Plasma IL-8 signature correlates with pain and depressive symptomatology in the study cohort. CONCLUSIONS: Overall, these findings indicate that plasma IL-8 profiles are dysregulated in BMS and that modulation of IL-8 production in the disorder may be a tool in the management of BMS symptomatology.

Treatment modalities for burning mouth syndrome: a systematic review.

OBJECTIVES: In the burning mouth syndrome (BMS), patients experience a burning sensation in the oral cavity with no associated injury or clinical manifestation. The etiology of this condition is still poorly understood, and therefore, treatment is challenging. The aim of this study is to perform a systematic review of treatment possibilities described in the literature for BMS. MATERIALS AND METHODS: PubMed, Embase, and SciELO databases were searched for randomized clinical trials published between 1996 and 2016. RESULTS: Following application of inclusion and exclusion criteria, 29 papers were analyzed and divided into five subcategories according to the type of treatment described: antidepressants, alpha-lipoic acid, phytotherapeutic agents, analgesic and anti-inflammatory agents, and non-pharmacological therapies. In each category, the results found were compared with regard to the methodology employed, sample size, assessment method, presence or absence of adverse effects, and treatment outcomes. CONCLUSIONS: The analysis revealed that the use of antidepressants and alpha-lipoic acid has been showing promising results; however, more studies are necessary before we can have a first-line treatment strategy for patients with BMS. CLINICAL RELEVANCE: To review systematically the literature about Burning Mouth Syndrome treatment may aid the clinicians to choose the treatment modality to improve patients symptoms based on the best evidence.

Clinical characterization and treatment outcome of patients with burning mouth syndrome.

Burning mouth syndrome (BMS) is a complex condition that affects the oral cavity, and data regarding effective treatment are limited. The purpose of this study was to explore the demographic and clinical information along with treatment outcomes for patients with BMS treated in a large referral center. Clinical records of the Oral Medicine Clinic at the University of Florida College of Dentistry were retrospectively searched for patients diagnosed between 2009 and 2014. Clinical data and treatment effectiveness were recorded. The records of 64 patients were included in this study. Women represented the majority of patients (81.2%), and the average age of all patients was 65 years. The most common systemic diseases were hypertension (59.4%), psycho-logical disorders (51.6%), and gastroesophageal reflux disease (50.0%). The majority of patients were taking 5 or more medications (70.3%). Treatment frequency and efficacy were as follows: a-lipoic acid, 47.5% frequency (57 prescribed treatments of 120 total treatments) and lasting improvement reported with 45.6% of prescribed treatments; clonazepam, 17.5% frequency (21/120) and improvement reported with 33.0% of prescribed treatments; oral disintegrating clonazepam, 15.8% frequency (19/120) and improvement reported with 52.6% of prescribed treatments; and topical vitamin E, 5.0% frequency (6/120) and improvement reported with 33.0% of prescribed treatments. Chi-square analysis indicated that a significantly better response to treatment was reported by women (P = 0.010) and patients who reported involvement limited to the tongue rather than multifocal oral involvement (P = 0.040); however, the significant relationships did not persist when the variables were evaluated together using logistic regression analysis. No other clinical or demographic features showed significant differences in response to treatment. Although treatment effectiveness in this study was variable and limited for some regimens due to infrequent usage, many of the patients reported alleviation of symptoms.

Serum zinc levels in 368 patients with oral mucosal diseases: A preliminary study.

BACKGROUND: The aim of this study was to assess the serum zinc levels in patients with common oral mucosal diseases by comparing these to healthy controls. MATERIAL AND METHODS: A total of 368 patients, which consisted of 156 recurrent aphthous stomatitis (RAS) patients, 57 oral lichen planus (OLP) patients, 55 burning mouth syndrome (BMS) patients, 54 atrophic glossitis (AG) patients, 46 xerostomia patients, and 115 sex-and age-matched healthy control subjects were enrolled in this study. Serum zinc levels were measured in all participants. Statistical analysis was performed using a one-way ANOVA, t-test, and Chi-square test. RESULTS: The mean serum zinc level in the healthy control group was significantly higher than the levels of all other groups (p < 0.001). No individual in the healthy control group had a serum zinc level less than the minimum normal value. However, up to 24.7% (13/54) of patients with AG presented with zinc deficiency, while 21.2% (33/156) of patients with RAS, 16.4% (9/55) of patients with BMS, 15.2% (7/46) of patients with xerostomia, and 14.0% (8/57) of patients with OLP were zinc deficient. Altogether, the zinc deficiency rate was 19.02% (70/368) in the oral mucosal diseases (OMD) group (all patients with OMD). The difference between the OMD and healthy control group was significant (p <0.001). Gender differences in serum zinc levels were also present, although not statistically significant. CONCLUSIONS: Zinc deficiency may be involved in the pathogenesis of common oral mucosal diseases. Zinc supplementation may be a useful treatment for oral mucosal diseases, but this requires further investigation; the optimal serum level of zinc, for the prevention and treatment of oral mucosal diseases, remains to be determined.

Temporomandibular disorders in burning mouth syndrome patients: an observational study.

BACKGROUND: Burning Mouth Syndrome (BMS) is a chronic disease characterized by absence of any lesions and burning of the oral mucosa associated to a sensation of dry mouth and/or taste alterations. The purpose of our study is to estimate signs and symptoms of Temporomandibular Disorders (TMD) in patients with BMS and to investigate for the existence of an association between BMS and TMD. MATERIALS AND METHODS: Forty-four BMS patients were enrolled; BMS subtype was established according to the classification of Lamey. After a gnathological evaluation, according to the protocol of the European Academy of Craniomandibular Disorders, patients were classified by RDC/TMD criteria. The data were compared and analyzed using a chi-square test to describe the existence of an association between BMS and TMD. RESULTS: 65.9% the BMS patients showed disorders classified as primary signs and symptoms of TMD according to RDC / TMD criteria, and 72.7% showed parafunctional habits. The chi-square test revealed a statistically significant association (p = 0.035) between BMS and TMD. CONCLUSION: The data suggest that there is a possible relationship not yet well understood between BMS and TMD, may be for neurophatic alterations assumed for BMS that could be also engaged in TMD pathogenesis.

Management of burning mouth syndrome taking into consideration various etiologic factors.

The aim of the research was to detect the stomatologic, endocrine and psycho-neurologic status in patients with burning mouth syndrome, elaborate different diagnostic criteria and effective therapy for the patients with burning mouth syndrome. 92 patients with burning mouth syndrome were studied. Patients ranged in age from 28 to 72 years. The conducted studies gave the possibility to make conclusions, the most important of which are: burning mouth syndrome (BMS) is not only stomatologic problem; this psychosomatic syndrome belongs to gerontologic disease and tendency of its "rejuvenation" was revealed as well (in the current study --2 women (28 and 32 year old, and 38 year old man); degree of revelation of the symptoms of depression, anxiety, obsession and somatization is closely related with duration of the diseases. These symptoms are progressing together with aging and reach the peak at 60-70 years old. Individual scheme of therapy was developed on the background of clinico-paraclinical study.

Evaluation of peripheral nerve fibers and mast cells in burning mouth syndrome.

Emerging evidence has revealed a cross-talk in the etiopathogenesis of burning mouth syndrome (BMS) related to peripheral nerve fibers (NF) and neuropeptides secreted by mast cells. Here, we investigated the S-100+ density and PGP 9.5+ integrity of peripheral NF and the tryptase+ mast cell density in the oral mucosa of BMS patients and healthy individuals. A total of 23 oral mucosa specimens (12 BMS and 11 controls) were evaluated. The clinical diagnosis of BMS was based on a careful examination, excluding other local and systemic causes. Samples were taken from an incisional biopsy of the tongue mucosa of individuals with symptomatic BMS, while the margins of the non-neoplastic tongue biopsy served as controls of healthy individuals. Immunohistochemistry was performed to determine the density/mm2 of S-100+, PGP 9.5+ peripheral NF, and tryptase+ mast cells. Similar densities of S-100+, PGP 9.5+ peripheral NF, and tryptase+ mast cells were found in cases of BMS, with a median value of 3.70, 0.70, and 29.24/mm2, respectively, and in the control group, with a median value of 2.60, 0.80, and 26.01/mm2, respectively (p > 0.05). Moreover, the relationship between S100+ and PGP 9.5+ peripheral NF was the same in both groups (p = 0.70). This study demonstrated that there were no alterations in the density and integrity of peripheral NF in the tongue of symptomatic BMS patients. However, the sensitization of peripheral NF in this disease may not depend on mast cell density.

Fungiform papillae density in patients with burning mouth syndrome and xerostomia.

OBJECTIVE: The aim of this study was to analyze fungiform papillae density in patients with burning mouth syndrome (BMS) and xerostomia. STUDY DESIGN: In this cross-sectional clinical study, sixty patients were included (20 with BMS, 20 with xerostomia and 20 healthy controls). The fungiform papillae density was analyzed over a small region on the anterior tip of the tongue with the aid of a digital camera. The number of papillae was measured in an area of 19 mm². RESULTS: The patients with BMS showed significantly higher fungiform papillae density than the patients with xerostomia; though no statistically significant differences were recorded versus the control group. In the BMS group, 65% of all cases presented a density of 71-90 papillae (within an area of 19 mm²), while 10% had more than 90 papillae. On the contrary, 70% of the patients with xerostomia had fewer than 70 papillae in the studied area. CONCLUSIONS: The digital camera offers a rapid, noninvasive and relatively simple way to study fungiform papillae density. The patients with BMS have higher fungiform papillae density than the patients with xerostomia.

Exfoliative cytology of the oral mucosa in burning mouth syndrome: a cytomorphological and cytomorphometric analysis.

OBJECTIVE: The aim of this study was to evaluate oral epithelial cells by exfoliative cytology in burning mouth syndrome (BMS). MATERIAL AND METHODS: Oral smears were collected from clinically normal-appearing mucosa by liquid-based exfoliative cytology in 40 individuals (20 BMS patients and 20 healthy controls matched for age and gender) and analysed for cytological and cytomorphometric techniques. RESULTS: Mean values of nuclear area (NA) for experimental and control groups were, respectively, 67.52 and 55.64 µm² (p < 0.05). Cytoplasmic area (CA) showed the following mean values: 1258.0 (experimental) and 2069.0 µm² (control). Nucleus-to-cytoplasm area ratio for the experimental group was 0.07, besides the control group was 0.03 (p < 0.05). Morphologically, oral smears exhibited normal epithelial cells in both experimental and control groups. There was a significant predominance of nucleated cells of the superficial layer in the smears of BMS patients (p = 0.00001). CONCLUSION: This study revealed that oral mucosa of BMS patients exhibited significant cytomorphometric changes in the oral epithelial cells. These changes probably are associated with epithelial atrophy and a deregulated maturation process that may contribute to the oral symptoms of pain and discomfort in BMS.

Chemosensory Function in Burning Mouth Syndrome a Comparative Cross-Sectional Study.

Taste and smell are considered to be functions that contribute to the maintenance of good nutritional status. The present study evaluates taste and smell function in patients with burning mouth syndrome (BMS) versus a control group. A cross-sectional study was made of 36 consecutive patients with BMS and 56 healthy patients. Smell was assessed using the Sniffin' Sticks test, while taste was evaluated with Taste Strips. Oral quality of life was assessed with the Oral Health Impact Profile-14 (OHIP-14), and the severity of dry mouth with the Thompson Xerostomia Inventory. The patients with BMS had a mean age of 60.4 0 ± 10.5 years, while the controls had a mean age of 61.3 ± 19 years. No significant differences in smell were recorded between the two groups. In contrast, significant differences in taste function were observed between the patients with BMS and the controls. In the patients with BMS, 44.4% suffered taste alterations compared with the 3.4% healthy controls. Further studies in such patients are needed to allow improved management of the chemosensory problems, mouth dryness, and oral health-related quality of life in BMS.

Prediction of treatment outcome in burning mouth syndrome patients using machine learning based on clinical data.

The purpose of this study is to apply a machine learning approach to predict whether patients with burning mouth syndrome (BMS) respond to the initial approach and clonazepam therapy based on clinical data. Among the patients with the primary type of BMS who visited the clinic from 2006 to 2015, those treated with the initial approach of detailed explanation regarding home care instruction and use of oral topical lubricants, or who were prescribed clonazepam for a minimum of 1 month were included in this study. The clinical data and treatment outcomes were collected from medical records. Extreme Gradient-Boosted Decision Trees was used for machine learning algorithms to construct prediction models. Accuracy of the prediction models was evaluated and feature importance calculated. The accuracy of the prediction models for the initial approach and clonazepam therapy was 67.6% and 67.4%, respectively. Aggravating factors and psychological distress were important features in the prediction model for the initial approach, and intensity of symptoms before administration was the important feature in the prediction model for clonazepam therapy. In conclusion, the analysis of treatment outcomes in patients with BMS using a machine learning approach showed meaningful results of clinical applicability.

Measuring the impact of oral mucosa disease on quality of life.

Our objective was to study the quality of life in patients with oral mucosa disease. Two hundred sixteen consecutive patients with oral pathology were studied at the Department of Oral Medicine, University of Murcia (Spain). Sixty patients had burning mouth syndrome, 100 oral lichen planus, 41 recurrent aphthous stomatitis and 15 had and other oral mucosa disorders. The instruments applied were the Spanish version of the SF-36, used to evaluate general quality of life, and the OHIP-49, Spanish version, to measure oral health-related quality of life. With respect to oral quality of life (OHIP-49 all items), the worst scores were found for burning mouth syndrome. The group formed by other mucosal lesions presented the lowest scores for the domains role physical and general health in the SF-36. Oral mucosa diseases have a negative impact on health and quality of life. Administration of specific and generic questionnaires provides a detailed picture of the impact of oral diseases on patients, which adds information that may be useful in clinical practice.

Oral microcirculation observed in vivo by videocapillaroscopy: a review.

Capillaroscopy is a non-invasive diagnostic technique that is fundamental in viewing peripheral circulation and in studying microangiopathies. The morphological study of microcirculation is of fundamental importance, mainly because the microvascular bed is directly involved in the etiopathogenesis of autoimmune disorders and acute and chronic inflammatory pathological conditions. The value of capillaroscopic investigation as a diagnostic means in cases of peripheral microcirculation disorders has been confirmed by numerous studies. Other studies used capillaroscopic investigations to evaluate microcirculation damage not as a complication of disease (diabetes), but as its initial stage, and therefore to make a diagnosis. Capillaroscopy is an interesting method of studying microcirculation, because of the possibility of studying small vessels in vivo by means of a microscope. Today, it has become more reliable, thanks to the development of observation tools (photography, videomicroscopy). This review describes in detail various aspects of the microcirculation of the oral mucosa.

Burning mouth syndrome and psychological disorders.

Burning mouth syndrome (BMS) is an oral dysaesthesia that causes chronic orofacial pain in the absence of a detectable organic cause. The aetiology of BMS is complex and multifactorial, and has been associated in the literature with menopause, trigger events and even genetic polymorphisms. Other studies have found evidence for mechanisms such as central and peripheral nervous system changes, with clinical and laboratory investigations supporting a neuropathologic cause. These physiological explanations notwithstanding, there is still much evidence that BMS aetiology has at least some psychological elements. Somatoform pain disorder has been suggested as a mechanism and factors such as personality, stress, anxiety, depression and other psychological, psychosocial and even psychiatric disorders play a demonstrable role in BMS aetiology and symptomatology. In order to treat BMS patients, both physiological and psychological factors must be managed, but patient acceptance of possible components of psychological disease basis is a major hurdle. Clinical signs of patient stress, anxiety or depression are a useful reinforcement of clinical discussions. The current paper proposes a number of clinical signs that may be useful for both clinical assessment and subsequent patient discussions by providing visible supportive evidence of the diagnosis.

Subgemmal neurogenous plaque associated with burning tongue: report of two cases and review of the literature.

Subgemmal neurogenous plaques, biphasic structures with a neurofibroma and neuroma patterns, are observed in tongue biopsies involving subepithelial areas, being characterized as aggregates of nerve plexus and ganglion cells. Oral burning symptoms, having many possible causes, are commonly observed during oral medicine practice, but the association of subgemmal neurogenous plaque with tongue burning symptoms is very unusual. Reported here are two cases of focal burning sensation in the lateral border of the tongue diagnosed as subgemmal neurogenous plaque through biopsy. Recognizing this entity is important to avoid misdiagnosis of other neural proliferations, especially in cases involving focal tongue burning.

Burning mouth syndrome: an evaluation of in vivo microcirculation.

BACKGROUND: Burning mouth syndrome (BMS) is an atypical orofacial algesic syndrome. The aim of the authors' research was to investigate the morphological characteristics of peripheral blood circulation in patients with BMS in comparison with those of the peripheral blood circulation in healthy people. METHODS: The authors examined 28 subjects, of whom 14 (10 women and four men) had BMS and 14 (nine women and five men) were healthy control subjects. They performed videocapillaroscopic examination with a capillaroscope with a fiber-optic probe at a magnification of x200, which allowed them to examine the morphological characteristics within the capillaroscopic area accurately. RESULTS: The capillaroscopic examination provided important diagnostic results regarding alterations of the local microcirculation in subjects with BMS when compared with healthy subjects. The results also showed a statistically significant increase in the diameter of the capillary ansae, afferent ansae and efferent ansae in subjects with BMS compared with subjects in the control group (P = .05). CONCLUSION AND CLINICAL IMPLICATIONS: The results revealed a vascular involvement in BMS. This information could improve the understanding of etiopathogenetic factors and aid in the development of therapeutic strategies for treating this disorder.

Treatment of smarting symptoms in the oral mucosa by appliance of lingual acrylic splints.

UNLABELLED: The aim of the present study was to evaluate the relieving effect on smarting symptoms in the oral mucosa by the use of lingual acrylic splints. Recruited for the study were 53 persons, 48 women and 5 men, with smarting symptoms in the oral mucosa, not associated with general disease, and with signs of erythema, most often on the apex of the tongue, and/or crenated tongue. Symptoms were registered from the tongue in 49 cases, the palate in 28 cases and the lips in 15 cases. A lingual acrylic splint was applied in the lower jaw behind the front teeth, not covering the occlusal surfaces and it was kept in the mouth day and night. At an average the splint was used in 8 months. A group of 10 women was recruited for comparison. These women were just instructed to avoid tongue pressing for at least a two month period. All patients were asked whether the treatment affected the symptoms and they registered their opinion on a 100 mm VAS line with end effect points "not helped at all/deteriorated" and "now completely without symptoms". On the question whether the treatment had affected the symptoms, the average result was 55 mm and median value 64 mm. The treatment results were somewhat better among those with moderate initial symptoms compared to those with severe symptoms. Interestingly, in the group for comparison, symptom VAS values improved significantly from 60 to 41 mm (P < 0.05). CONCLUSION: Treatment of smarting symptoms in the oral mucosa may to a great extent be relieved by the application of an acrylic lingual splint. However, before using this splint method, an effort should be made to make the patient actively avoid tongue pressure.

Evaluation of the effect of melatonin in patients with Burning mouth syndrome: a double-blind, placebo-controlled randomized clinical trial

Abstract The present study was carried out to evaluate the effect of Melatonin and Placebo in the patient with the Burning mouth (BMs). This double-blind, placebo-controlled randomized clinical trial study was carried out on 30 patients who were suffering from BMS. During this period patients were divided into 2 study and control groups. The study group used four 3 mg Melatonin daily and the control group received a placebo. Then the severity of the burning sensation was measured by the physician Sleep quality was measured using the VAS scale using the Petersburg questionnaire. Data in the application Enter SPSS 20 and then using T test or equivalent Nonparametric was analyzed, mean sleep score and mean severity of oral irritation before and after treatment in two the group was evaluated using T-test Independent. Level significance was considered 0.05. The results of the present study show that the use of melatonin and a placebo in patients with BMS reduces sensation and improves their sleep quality, although it may not reduce it completely. In this study severity of burning was 4.93±2.56 after treatment in the study group and 6.93±2.12 in the control group, which was statistically significant (P =0.036). No significant difference was observed between the two groups in the sleep quality score (P-value = 0.43). Using Melatonin can be a reliable way to treat pain for which there is no standard treatment to date. Although evidence suggests an association between sleep disorders and BMS, melatonin was not superior to a placebo in reducing BMS-induced burning in the present study. Identification of stressors and the ways to struggle with them, further studies with larger samples and higher oral doses, extended follow-up periods and control of psychological factors, and measurement of body mass index that may affect pharmacokinetics are recommended.

Management of reticular oral lichen planus patients with burning mouth syndrome-like oral symptoms: a pilot study.

OBJECTIVES: We sought to determine the efficacy of psychotropic drug in the management of BMS-like oral symptoms in patients with reticular oral lichen planus (R-OLP) refractory to conventional therapies, and its impact on anxious and depressive symptoms. MATERIALS AND METHODS: We enrolled 28 cases of symptomatic R-OLP. The Numeric Rating Scale (NRS), the Total Pain Rating Index (T-PRI), the Hamilton rating scales for Depression (HAM-D) and Anxiety (HAM-A) were performed at baseline (time 0), after 2 months of topical clonazepam (time 1) and after 6 months of benzodiazepine and antidepressant drugs (time 2). RESULTS: R-OLP patients showed a statistically significant improvement in the NRS and T-PRI scores from time 0 [median: 9.0 (IQR: 7.2-10.0) and 10.5 (IQR: 7.0-13.0), respectively] to time 2 [(median: 2.0 (IQR: 2.0-3.0) (p < .001) and 3.0 (IQR: 2.0-4.7) (p < .001), respectively]. Similarly, the HAM-A and HAM-D scores showed an improvement from time 0 [(median: 15.0 (IQR: 10.2-17.8) and 13.0 (IQR: 12.0-15.0), respectively] to time 2 [median: 6.0 (IQR: 4.0-7.0) (p < .001) and 5.5 (IQR: 4.25-6.0) (p < .001), respectively]. CONCLUSIONS: Psychotropic drugs turned out to be effective in the management of BMS-like oral symptoms in R-OLP patients refractory to conventional immunosuppressive therapy, although in a long-term period.