Serum zinc levels in patients with burning mouth syndrome

The serum zinc levels were measured by atomic absorption spectrophotometry in 30 patients with burning mouth syndrome, (BMS) and in 30 control subjects with clinically healthy oral mucosa. The mean value of serum zinc levels in the patient group was found to be significantly lower (mean +/- SD = 12.13 +/- 1.40 mumol/L) than the mean value of serum zinc levels in the control group (mean +/- SD = 12.89 +/- 1.62 mumol/L; p less than 0.05). The number of subjects with serum zinc levels less than the minimum normal value (less than 11 mumol/L) was higher in the patients with BMS (30%) than in the control subjects (10%). These results suggest that in some patients low serum zinc levels may be associated with BMS. However, the number of patients with BMS was too small to allow definite conclusions.     

Burning mouth syndrome and saliva: detection of salivary trace elements and cytokines

Background: Burning mouth syndrome (BMS) is considered a syndrome with an unknown cause. Roles of various trace elements and cytokines in saliva have been implicated in the development of BMS. The aim of the present study was to compare the levels of salivary trace elements [magnesium (Mg), zinc (Zn), copper (Cu)] and interleukin (IL)‐2 and IL‐6, and to search for a correlation between depression/anxiety and salivary trace elements and cytokines in BMS patients and controls. Methods: Thirty patients with BMS and 30 matched healthy controls participated in the study. Unstimulated saliva was collected from participants and salivary flow rates were determined. Mg, Zn and Cu levels were determined by atomic absorbance spectrophotometry. Cytokine immunoassay kits were used to determine the concentration of IL‐2 and IL‐6 in the whole saliva samples. Anxiety and depression were analyzed by means of the Speilberger State‐Trait Anxiety Inventory (SAI‐TAI) and Zung Self‐Rating Depression Scale. Results: Although subjects in the control group had significantly higher mean levels for Mg compared with BMS patients (P < 0.01), no statistically significant differences were observed in relation to Zn and Cu levels between the two groups (P < 0.001). There were no statistically significant differences in IL‐2 and IL‐6 levels of BMS and control groups, but subjects in BMS group had slightly, not significantly, higher mean levels for IL‐6 compared with controls. Subjects in BMS group had significantly higher mean values for TAI compared with controls (P < 0.05). There were no statistically significant differences in relation to salivary levels of Mg, Zn, Cu, IL‐2, IL‐6 and depression/anxiety between BMS and control groups. Conclusions: The results of our study indicate that Mg levels could have an impact on symptoms of BMS and further studies are necessary to determine the importance of cytokines in the pathogenesis of BMS.     

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.     

Neuropeptides in saliva of subjects with burning mouth syndrome: a pilot study

Oral Diseases (2010) 16 , 365–374 Objective: A neuropathic basis has been suggested for burning mouth syndrome (BMS) and an altered concentration of neuropeptides has been reported in lingual oral mucosa and saliva in this disease. The aims of this study were to compare the levels of nerve growth factor (NGF), substance P (SP) and degranulation products from mast cells and neutrophils in the saliva of BMS subjects with those of control subjects. Material and Methods: Salivary flow rate, protein concentration, NGF peptide and mRNA, SP, mast cells tryptase, neutrophil myeloperoxidase and calprotectin were analyzed in saliva of 20 BMS subjects and of 20 age‐ and gender‐matched healthy subjects. Results and Conclusions: NGF peptide and tryptase activity were shown to be significantly and persistently higher in saliva of BMS subjects, with respect to control values. Conversely the salivary levels of SP were shown to be significantly lower, while neutrophil markers didn’t show any change. We conclude that the neuropathic origin of the disease is confirmed at salivary level. Furthermore, the higher tryptase activity indicates a possible involvement of mast cells. The salivary neuropeptide concentration in BMS subjects, together with mast cell derived compounds, could be useful biomarkers for diagnosis and monitoring of this disease.     

Evidence of chorda tympani dysfunction in patients with burning mouth syndrome

BACKGROUND: More than two-thirds of patients with burning mouth syndrome (BMS) have altered taste sensation. The authors conducted a study to assess chorda tympani and trigeminal nerve function in these patients. METHODS: The study was composed of 48 patients; 22 were diagnosed as having BMS, 14 had burning symptoms related to other diseases and were diagnosed as having secondary burning mouth syndrome (SBMS), and 12 were healthy volunteers. The authors evaluated the electrical detection thresholds of the infraorbital and mental nerves and the electrical taste and electrical detection/tingling thresholds in the anterior two-thirds of the tongue for all patients. Electrical taste threshold is thought to be dictated by chorda tympani nerve function while electrical detection/tingling thresholds are regulated by trigeminal nerve function. RESULTS: The mean electrical taste/tingling detection thresholds ratio and the taste detection thresholds were significantly higher in patients with BMS than in patients with SBMS and in control subjects, indicating chorda tympani nerve dysfunction. Eighteen (82 percent) of the 22 patients with BMS demonstrated chorda tympani dysfunction (13 unilateral and five bilateral). CONCLUSIONS: Chorda tympani hypofunction may play an important role in BMS pathology. Unilateral hypofunction may be sufficient to produce generalized burning sensation exceeding the affected nerve area. CLINICAL IMPLICATIONS: Elevated taste detection threshold levels determined via electrogustatory testing and an elevated taste/tingling detection thresholds ratio may assist clinicians in the diagnosis of BMS. More studies are needed to validate these findings.     

Calcitonin gene-related peptide in gingival crevicular fluid in periodontal health and disease

The aims of the present study were to investigate whether calcitonin gene-related peptide (CGRP) was present in gingival crevicular fluid in both periodontal health and disease and to study the relationship with periodontal inflammation. Gingival crevicular fluid (GCF) was collected from a healthy, a gingivitis and a periodontitis site in 18 subjects with periodontitis and from a healthy site in 19 subjects without periodontitis. The volume of GCF was measured and each sample subsequently analysed for CGRP by radioimmunoassay. In subjects with periodontitis, CGRP immunoreactivity (CGRP-IR) was not detected in any periodontitis sites, nor in 67% of gingivitis and 28% of periodontally-healthy sites. The total amount of CGRP-IR was significantly elevated in periodontally healthy (p=0.0015) and gingivitis (p=0.027) compared with periodontitis sites. CGRP-IR was present in 89% of the healthy sites sampled in control subjects at comparable levels to those in healthy sites in periodontitis subjects. It is concluded that in periodontal inflammation, particularly in deep pockets, constituents of GCF process and degrade CGRP.     

女性灼口综合征的性激素水平检测

目的：探讨女性灼口综合征（BMS）患者体内性激素和皮质激素水平的改变与临床症状之间的关系。方法：采用放射免疫分析方法，对60例女性BMS患者血清中的8种性激素及皮质激素水平进行测定，并以20例正常女性对照。结果：BMS组睾酮、雄烯二酮、硫酸脱氢表雄酮均高于对照组（P＜0．01）；雌二醇、孕酮、泌乳素、卵泡刺激素、黄体生成素无明显变化（P＞0．05）；睾酮／雌二醇的比值明显升高。结论：睾酮／雌二醇的比值明显升高表明雌激素的相对升高或者是雌激素的相对减少。提示在临床考虑BMS的治疗 方案时可以给患者服用一定量的雌激素以维持睾酮／雌二醇比值平衡，减轻临床症状。     

Oral pain perception and taste in Burning Mouth Syndrome

J Oral Pathol Med (2010) 39 : 22–27
Background:  Aim of this study was to investigate the effect of idiopathic burning mouth syndrome (BMS) on both, the pain perception within trigeminal lingual nerve distribution and gustatory sensitivity using capsaicin threshold test, and regional taste tests, respectively.
Methods:  Pain thresholds for capsaicin were assessed using capsaicin-impregnated filter-paper strips. The strips were placed midline on the tongue tip for whole mouth testing with the mouth closed, and on the left or right edge of the extended anterior tongue for lateralized testing. Measures of gustatory function were obtained by validated "taste strips" test kit and electrogustometry. The tests were applied to 13 patients with BMS. Results were compared with those from 28 healthy subjects.
Results:  Patients with BMS exhibited a decreased gustatory and somatosensory perception compared with healthy controls. These changes were found for lateralized tests but not for the whole mouth test procedure. Duration of disorder showed an effect on the capsaicin threshold, with patients being less sensitive to capsaicin exhibiting an increased duration of disorder.
Conclusion:  Both pain-related and gustatory sensitivies of the tongue are found to be decreased in BMS.     

A literature review and pilot study to characterise the treatment of burning mouth syndrome.

Although the definition of burning mouth syndrome (BMS) can vary, the most commonly accepted is that of a burning sensation of normal appearing oral mucosa with no apparent underlying local or systemic contributing factors. The condition can be classified according to the patterns of burning experienced, the severity of the burning, as well as the pattern of onset. The management of these patients is difficult, since they are often seen by numerous clinicians and many unnecessary tests are performed in the hope of finding an underlying physical cause for the burning. No precise information pertaining to the natural history of BMS could be found. This paper consists of a selective review of the literature on BMS as well as a pilot study involving the standardised collection of data on 10 patients (9 women and 1 man) with BMS. These patients will be followed up in the long term in order to gather information pertaining to the natural history of this condition. No detectable local or systemic cause for the burning sensation could be found for any of the 10 subjects. The role of somatisation as a mechanism for burning sensation was investigated and certain proposals have been put forward regarding the management of such patients.     

灼口综合征三叉神经诱发电位的初步研究

目的 通过电生理学手段检测BMS患者痛阈值,记录三叉神经诱发电位变化,以期推测神经传导过程中的病理状态,进一步探讨其发病机制。方法 以神经肌电图仪刺激患者舌背,共记录38个样本（灼痛者22,麻胀者10,对照组6）感知最小刺激量为痛阈,3倍阈值刺激舌神经,记录诱发电位中N3、N4的潜伏期及高峰电位的出现时间。结果 灼痛组痛阈值降低,N3、N4潜伏期缩短,高峰电位出现明显提前,与其他两组比较具有显著性差异（P＜0.01）,麻胀组则呈相反趋势,与对照组比较无显著差异（P＞0.05）。结论 BMS灼痛者神经兴性提高,对外界刺激易感;麻胀组则可能存在神经部分或安全传导阻滞。说明BMS灼痛报告真实可信,同时反映出神经传导过程中病理状态存在的可能性,显示出BMS可能存在的发病机制。     

Biochemical analysis of saliva and taste acuity evaluation in patients with burning mouth syndrome, xerostomia and/or gustatory disturbances

OBJECTIVE: In the current study, we performed taste and salivary analysis on patients suffering from burning mouth syndrome and xerostomia or taste disturbances. STUDY DESIGN: A total of 180 patients who complained of idiopathic burning mouth syndrome (BMS) and taste aberrations and/or xerostomia that may accompany BMS were evaluated. These patients were compared with 90 healthy, age- and sex-matched controls. Salivary flow rate, biochemical and immunological analysis and taste acuity by the forced-choice drop technique were performed for all subjects. These analyses were found to be conclusive in distinguishing controls from patients with complaints. RESULTS: The great similarity of both salivary and taste analysis in the BMS, taste aberration and xerostomia groups, which were significantly different from the results obtained in the control group, was found to be the most striking result. Higher salivary concentrations in the experimental group were consistent with a lower saliva (water) flow rate. CONCLUSION: An oral neuropathy and/or neurological transduction interruption induced by salivary compositional alterations is suggested as the possible aetiology for the complaints. This report may add an important objective diagnostic tool to the clinician treating these patients.     

Carboxypeptidase‐mediated metabolism of calcitonin gene‐related peptide in human gingival crevicular fluid – a rôle in periodontal inflammation?

Background: Metabolism by peptidases plays an important rôle in modulating the levels of biologically‐active neuropeptides. The metabolism of the anti‐inflammatory neuropeptide calcitonin gene‐related peptide (GCRP), but not the pro‐inflammatory neuropeptides substance P (SP) and neurokinin A (NKA) by components of the gingival crevicular fluid (GCF), could potentiate the inflammatory process in periodontitis. Aims: To characterise the extracellular hydrolysis of CGRP as a mechanism for the selective inactivation of this neuropeptide in GCF from periodontitis sites. Methods: Samples of GCF from periodontitis patients and periodontally‐healthy subjects were incubated with synthetic human SP, NKA or CGRP. Reaction between the GCF constituents and synthetic peptides was allowed to progress from 0–180 min. Results of neuropeptide metabolism at each time were analysed by matrix‐assisted laser desorption/ionisation mass spectrometry. Results: There was no evidence of metabolism of SP, NKA or CGRP by constituents of healthy GCF. Metabolism of synthetic SP and NKA was minimal even after extensive incubation with periodontitis GCF. However, loss of carboxy‐terminal amino acids was evident after only 1 min incubation with periodontitis GCF. The pattern of CGRP metabolism, which proceeded from the C‐terminus, indicated that the neuropeptide was degraded by a carboxypeptidase. After 180 min, there was extensive carboxypeptidase degradation of CGRP to an 11 amino acid peptide. Conclusions: It is concluded that carboxypeptidase activity in GCF from periodontitis patients is responsible for rapid breakdown of CGRP but not SP or NKA. The rapid action of this carboxypeptidase on the anti‐inflammatory neuropeptide CGRP is suggestive of a pathophysiological rôle for the enzyme in selectively degrading CGRP, thereby potentiating periodontal inflammation.     

Cognitive profile of patients with burning mouth syndrome in the Japanese population

The present study investigated which cognitive characteristics, including cancer phobia, self-efficacy, pain-related catastrophizing, and anxiety sensitivity, affect burning mouth syndrome (BMS) symptoms in the Japanese population. A total of 46 BMS patients (44 women and 2 men; mean age, 59.98 ± 9.57 years; range, 30–79 years) completed a battery of questionnaires, including measures of pain severity, oral-related quality of life (QOL), stressresponse, pain-related catastrophizing, self-efficacy, anxiety sensitivity, and tongue cancer phobia. The Pain Catastrophizing Scale (PCS), General Self-Efficacy Scale (GSES), and Anxiety Sensitivity Index (ASI) scores in the BMS patients were compared with the scores of Japanese healthy participants (PCS, n = 449; GSES, n = 278; ASI, n = 9603) reported in previous studies. Catastrophizing and anxiety sensitivity were significantly higher in the BMS patients than in the healthy subjects (P < 0.001). In BMS patients, catastrophizing was significantly correlated with pain severity, stress-response, psychological disability, social disability, and handicap. Cancer phobia was significantly correlated with psychological disability and handicap. Since catastrophizing showed a higher correlation with BMS symptoms than cancer phobia, catastrophizing might be a more significant cognitive factor affecting symptoms than cancer phobia in BMS patients in the Japanese population.     

Distinguishing patients with glossopyrosis from those with oropyrosis based upon clinical differences and differences in saliva and erythrocyte magnesium

ObjectiveBurning mouth syndrome (BMS) is a complex of clinical symptoms defined by burning sensations in the oral cavity without observed oral pathology. Clinically two patient groups within BMS were distinguished, one with burning limited to the anterior tongue (glossopyrosis) and the other with burning in multiple mouth regions, including tongue, lips, palate, gums and cheeks (oropyrosis). Biochemical differences between these two groups could assist in distinguishing them.DesignEighty-three patients with BMS, 47 with oropyrosis and 31 with glossopyrosis were studied. Measurements of zinc, copper, magnesium and calcium in blood plasma, erythrocytes and parotid saliva were obtained in patients and in normal subjects and mean levels were compared.ResultsClinical history differentiated patients into categories of oropyrosis and glossopyrosis. Erythrocyte and saliva levels of magnesium were significantly lower in patients with glossopyrosis than in patients with oropyrosis or in normal volunteers whereas levels of zinc and calcium were similar.ConclusionsThese data suggest that patients with glossopyrosis not only differ clinically from those with oropyrosis but also exhibit magnesium deficiency as manifested by lower than normal magnesium levels in saliva and erythrocytes. Lingual burning in patients with glossopyrosis is consistent with hyperalgesia and neurogenic inflammation observed in patients and animals with magnesium deficiency and in magnesium deficient tissues. These results suggest a possible biochemical mechanism for pyrosis in patients with glossopyrosis.     

Relationship of calcitonin gene-related peptide in synovial tissues and temporomandibular joint pain in humans

OBJECTIVE: To elucidate the expression of calcitonin gene-related peptide (CGRP) in synovial tissue taken from the human temporomandibular joint (TMJ) with internal derangement, and discuss the relationship between CGRP and joint pain. STUDY DESIGN: Using an immunohistochemical technique, 48 joints in 48 patients were examined. As controls, synovial tissue specimens from 7 joints with habitual dislocation without pain were also examined. RESULTS: In all of the internal derangement and control subjects, CGRP-positive cells were observed in the connective tissues around the blood vessels beneath the lining cells. The extent score of CGRP was significantly higher in the internal derangement group than in the control group (P=.033). There was a significant positive correlation between the extent score of CGRP and joint pain (P=.036, r=0.30). CONCLUSIONS: These results suggest that the expression of CGRP is increased in the synovial tissues from patients with internal derangement, and that CGRP seems to play an important role in the mechanism of pain production in patients with symptomatic internal derangement.     

Burning mouth syndrome: an update on diagnosis and treatment methods

Burning mouth syndrome is characterized by both positive (burning pain, dysgeusia and dysesthesia) and negative (loss of taste and paraesthesia) sensory symptoms involving the lips and tongue, mainly the tip and anterior two-thirds. BMS patients report a persistently altered (metallic) taste or diminished taste sensations. Acidic foods such as tomatoes and orange juice cause considerable distress. Most of the common laboratory tests suggested for BMS patients will be negative as well. BMS is best subcategorized as primary BMS, no other evident disease, and secondary BMS, which is defined as oral burning from other clinical abnormalities. The presence of BMS is very uncommon before the age of 30; 40 years for men. The onset in women usually occurs within three to 12 years after menopause, and is higher in women who have more systemic disease. Quantitative assessment of the sensory and chemosensory functions in BMS patients reveals that the sensory thresholds (significantly higher) are different than in controls. Tongue biopsies have shown that there is a significantly lower density of epithelial nerve fibers for BMS patients than controls. The above data generally support the idea that BMS is a disorder of altered sensory processing which occur following the small fiber neuropathic changes in the tongue. BMS patients frequently have depression, anxiety, sometimes diabetes, and even nutritional/mineral deficiencies, but overall these co-morbid diseases do not fully explain BMS. The management of BMS is still not satisfactory, but because BMS is now largely considered to be neuropathic in origin, treatment is primarily via medications that may suppress neurologic transduction, transmission, and even pain signal facilitation more centrally. Finally, spontaneous remission of pain in BMS subjects has not been definitely demonstrated. The current treatments are palliative only, and while they may not be much better than a credible placebo treatment, few studies report relief without intervention.     

Efficacy of moclobemide in burning mouth syndrome: a nonrandomized, open-label study

AIMS: To compare burning mouth syndrome (BMS) patients with age- and gender-matched controls for psychologic conditions, to analyze the effect of menstrual state on the intensity of burning, and to assess the efficacy of an antidepressant medication on the burning pain and psychologic status. METHODS: Ninety-four patients with BMS and 94 matched control subjects participated in the study. Anxiety and depression were analyzed by means of the Spielberger State-Trait Anxiety Inventory and Zung Self-Rating Depression Scale, and the severity of the burning sensation was measured by means of a visual analog scale (VAS). In female BMS patients and controls, the menstrual state was noted (menstruating, menopausal, or postmenopausal). BMS patients were treated with the antidepressant moclobemide (150 mg 2 times daily) for 3 months. Thereafter, anxiety, depression, and burning pain intensity were reassessed. Patient-perceived satisfactory improvement for burning sensation was assessed using a 5-point categorical rating of change scale. RESULTS: BMS patients had significantly higher anxiety and depression scores than controls (P < .05). After treatment, anxiety and depression scores as well as the VAS values for burning pain decreased significantly (P < .001). Thirty-seven patients reported good to very good improvement, and 44 reported satisfactory improvement. No adverse reactions were reported. CONCLUSIONS: The study confirmed earlier reports that BMS patients have higher anxiety and depression levels than controls. An antidepressant medication may be effective in alleviating the burning pain, at least in the short-term.     

Plasma and saliva levels of nerve growth factor and neuropeptides in chronic migraine patients

Oral Diseases (2011) 17 , 187–193 Objectives: To investigate the level and interrelationship of nerve growth factor (NGF) and sensory neuropeptides [substance P (SP), calcitonin gene‐related peptide (CGRP)] in plasma and saliva of chronic migraine patients, and to analyze the association between pain intensity and their concentration. Materials and methods: Plasma and resting whole saliva were collected from 33 chronic migraine patients and 36 control subjects. NGF, SP, and CGRP concentrations were measured by enzyme immunoassay and pain intensity of each subject was measured using the Graded Chronic Pain Scale. Results: Chronic migraine patients showed higher NGF and neuropeptide levels in both plasma and saliva compared to the control subjects. Plasma NGF, and plasma and saliva levels of SP and CGRP were highly associated with pain intensity. There was a significant positive correlation between NGF and both neuropeptide levels in plasma, and between the neuropeptide levels in both plasma and saliva. Plasma levels of SP and CGRP were significantly correlated with their saliva level. Conclusions: The increased production of NGF and sensory neuropeptides may play an important role in the maintenance of pain in chronic migraine and analysis results of human saliva could act as an index of disease state and therapeutic outcome.     

灼口综合征患者的疼痛与个性,情绪间因果关系的研究

为了深入了解灼口综合征（ＢＭＳ）精神因素个中性，情绪与疼痛间的淮因谁果的焦点问题，本研究选用了２８例病史较长，疼痛明显且高频复发的复发性阿弗它溃疡（ＲＡＵ）患才为对照，应用ＥＰＱ，ＳＣＬ－９０，ＬＥＳ三个量表了解ＲＡＵ患者与病较短的２９例ＢＭＳ患者间个性，情绪，应激三方面的差异性，结果显示在ＢＭＳ组较ＲＡＵ组个性偏内向，且精神质（Ｐ值）得分显著高于ＲＡＵ组，ＢＭＳ组经历的负性生活事件及多项情绪因子     

灼口综合征患者静态唾液流速和口干症状的相关研究

目的：探讨不同亚型灼口综合征（BMS）患者静态唾液流速有无差异以及静态唾液流速速与BMS患者口干症状之间有无相关性,方法：采用舌下置纱团浸唾称重法测定52例BMS患者和37例正常对照组的静态唾液流速,结果：BMS组的平均静态唾液流速较对照组低,但统计学上无显著差异。BMS的3个亚型间平均静态唾液流速无统计学上显著差异,具口干症状的BMS患者静态唾液流速与不具口干症状者差异亦不显著,结论：BMS患者口干症状与静态唾液流速之间的相关性不显著。