Pathogenesis Of Burning Mouth Syndrome Research Articles

Saliva and tongue microbiota in burning mouth syndrome: An exploratory study of potential roles.

Burning mouth syndrome (BMS) is a chronic orofacial pain disorder with unclear etiology, in which the tongue is most commonly affected. This study aims to provide implication of the possible relationship between oral microbiota and the pathogenesis of BMS. Saliva and tongue swabs of 15 primary BMS patients and 10 healthy controls were collected and assessed by 16S rRNA gene amplicon sequencing. The microbiota compositions were compared and bioinformatic analysis was conducted. Differences in microbiota compositions between BMS patients and healthy controls were revealed in both saliva and tongue samples. In saliva, Streptococcus, Rothia, and Neisseria were the predominant genus at the taxonomic level in BMS patients. In tongue samples, Prevotella, Streptococcus, and Neisseria were the dominant genus at thetaxonomic level in BMS patients. LEfSe analysis and linear discriminant analysis score showed that Actinobacteria were the predominant phylum in saliva, and Selenomonas were enriched in the dorsum of the tongue of BMS patients. This study for the first-time reported saliva and tongue microbiota profiles were distinguished from that of healthy controls, indicating a necessity for further research on the possible relationship between oral microbes and the pathogenesis of BMS.

Oxidative stress–mediated proapoptosis signaling: A novel theory on the mechanism underlying the pathogenesis of burning mouth syndrome

BackgroundBurning mouth syndrome (BMS) is a chronic oral pain disorder characterized by a generalized burning sensation in the oral mucosa without apparent medical or dental causes. Despite various hypotheses proposed to explain BMS pathogenesis, a clear understanding of the cellular-level events and associated histologic and molecular findings is lacking. Advancing our understanding of BMS pathogenesis could facilitate the development of more targeted therapeutic interventions. Types of Studies ReviewedThe authors conducted an extensive literature search and review of cellular mechanisms, focusing on evidence-based data that support a comprehensive hypothesis for BMS pathogenesis. The authors explored novel and detailed mechanisms that may account for the characteristic features of BMS. ResultsThe authors proposed that BMS symptoms arise from the uncontrolled activation of proapoptotic transmembrane calcium permeable channels expressed in intraoral mucosal nerve fibers. Elevated levels of reactive oxygen species or dysfunctional antiapoptosis pathways may lead to uncontrolled oxidative stress–mediated apoptosis signaling, resulting in upregulation of transmembrane transient receptor potential vanilloid type 1 and P2X 3 calcium channels in nociceptive fibers. Activation of these channels can cause nerve terminal depolarization, leading to generation of action potentials that are centrally interpreted as pain. Conclusions and Practical ImplicationsThe authors present a novel hypothesis for BMS pathogenesis, highlighting the role of proapoptotic transmembrane calcium permeable channels and oxidative stress–mediated apoptosis signaling in the development of BMS symptoms. Understanding these underlying mechanisms could provide new insights into the development of targeted therapeutic interventions for BMS. Additional research is warranted to validate this hypothesis and explore potential avenues for effective management of BMS.

The over-expression of miRNA-206 in peripheral blood of patients with burning mouth syndrome and its relationship with anxiety and depression.

Burning Mouth Syndrome (BMS) is characterized by persisting burning pain of the oral mucosa, and its etiopathogenesis remains poorly understood. Our study aimed to detect the expression of miRNA-206 in the blood and clarify the relationship among miRNA-206, pain, anxiety and depression of BMS patients. Thirty patients with BMS and 30 healthy individuals were enrolled in the experimental and control groups, respectively. Data on medical history and clinical oral examination for all participants were collected. Simultaneously, scores of Visual Analogous Scale (VAS), Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) were administered. The expression level of miRNA-206 in plasma were determined by RT-(q)PCR. Finally, and the relationship of miRNA-206 expression with the VAS score, SAS score, and SDS score was analyzed. χ2 test, t-test were used for statistical analysis of the data, and P < 0.05 was considered statistically significant. The majority of the patients with BMS identified the tongue as the main pain area, and showed dry mouth and poor sleep quality. The SAS and SDS scores of patients with BMS were higher than those of healthy controls (P <0.05) and were positively correlated with VAS pain score. In addition, miRNA-206 expression was higher in patients with BMS than in healthy individuals (P <0.05), and was positively correlated with the VAS and SDS scores (P < 0.05). Patients with BMS suffer from pain and tend to be more anxious and depressed than healthy controls. miRNA-206 expression in the peripheral blood of patients with BMS is positively correlated with pain and depression, which may be involved in the pathogenesis of BMS.

Effectiveness of Pregabalin in Treatment of Burning Mouth Syndrome

Background and Objectives Burning mouth syndrome (BMS) is a chronic pain disorder involving a burning sensation of the oral cavity without any identifiable oral lesion. According to the recent studies, the pathogenesis of BMS is presumed to be caused by a neuropathic condition. Gabapentin and pregabalin have been used for various neuropathic pains, but pregabalin has several pharmacokinetic advantages over gabapentin. To our best knowledge, there are no recent studies reported on the administration of pregabalin in treating BMS in Korea. Therefore, in this study, we investigated the therapeutic effect of pregabalin in treating BMS.Subjects and Method We chose as candidates 33 patients diagnosed as BMS and took pregabalin for more than four weeks. Pregabalin was administered at 75 mg once a day for 2 to 4 weeks at first, and then the dose was modified depending on whether or not symptoms improved. Effectiveness of treatment was evaluated in the way that the patients subjectively answered whether or not symptoms were improved.Results A total of 21 (63.6%) out of 33 patients were responsive to the treatment. Among those, at the last follow-up, 8 patients (38.1%) showed slight improvement, and 13 patients (61.9%) showed mostly improvement or disappearance of symptoms. The average time interval from starting pregabalin to the first symptom improvement was 50.1 days, and most patients showed symptom improvement within 8 weeks.Conclusion This study concludes that pregabalin can be added as a meaningful option in the treatment of BMS. The additional double-blind clinical study should be followed to further prove the effectiveness of pregabalin.

Comparative analysis of the oral microbiome of burning mouth syndrome patients

ABSTRACT Burning mouth syndrome(BMS) is a chronic pain condition accompanied by unpleasant burning sensationsof the oral mucosa. While multiple factors were proposed for the etiology, evidencesuggested a neuropathic pain origin while others suspected the use ofantibiotics as the underlying cause. Interestingly, several reports demonstratedthe intimate interaction of the nervous system and the microbiome. The currentstudy aims to elucidate the correlation of the oral microbiome with the pathophysiologyof the primary BMS. Microbiome samples obtained from the unstimulated wholesaliva of 19 primary BMS patients and 22 healthy controls were sequenced and analyzedof the V3-V4 region of 16S rRNA gene. There was a distinct difference in themicrobial composition between the BMS and the control groups at all taxonomic levels.Alpha diversity indexes of the oral microbiome were significantly lower in theBMS group. The samples were readily distinguished by multidimensional scalinganalysis and linear discriminant analysis effect size. Streptococcus, Rothia, Bergeyella, and Granulicatellagenus were dominant in the BMS group, while Prevotella, Haemophilus,Fusobacterium, Campylobacter,and Allorevotella genus were moreabundant in the healthy group. Distinct microbiome signatures of BMS patientssuggested a diagnostic value and a potential role in the pathogenesis of BMS.

Is Burning Mouth Syndrome a Neuropathic Pain Disorder? A Systematic Review.

To conduct a systematic review compiling an update on the pathophysiology of burning mouth syndrome (BMS) by reviewing the theories and studies published in the last 5 years that consider BMS a neuropathic disease. A literature review was carried out in April 2020 on the PubMed database by using the following MeSH terms: "(burning mouth OR burning mouth syndrome OR burning mouth pain OR sore mouth OR burning tongue OR oral neuropathic pain OR glossodynia OR stomatopyrosis) AND (etiopathogenesis OR etiopathological factors OR etiology)." The research carried out according to the methodology found 19 case-control studies (1 of which was in vivo) and 1 RCT. Of the 19 included studies, 8 showed an evidence score of 2-; 8 showed 2+; another 2 showed 2++; and 1 showed 1+. Quality studies on this topic are insufficient and heterogenous. In the pathogenesis of BMS, both peripheral and central neuropathies appear to play a pivotal role. Nevertheless, the balance between them varies from case to case and tends to overlap. BMS does not seem to be a result of direct damage to the somatosensory nervous system, but a dysfunction in it and in the brain network.

Burning mouth syndrome and squamous cell carcinoma: Coincidence or a new disease association

Burning mouth syndrome (BMS) is described as a burning feeling or sensation in the mouth in the absence of specific oral mucosa lesions. Patients with BМS often complain of paraesthesia (tingling sensation in the mouth), xerostomia (dry mouth sensation), changes in sense of taste and smell. In the past two decades, significant research of this condition has been conducted. Psychological, systemic and local factors probably play a role in the pathogenesis of BMS. We present a case of an 82-year-old female with burning sensation in the mouth and a coexisting growing lesion on her lower lip.

Cytokine levels and their role in the etiopathogenesis of Burning Mouth Syndrome: A systematic review.

Burning Mouth Syndrome is characterized by variable symptoms that include pain, burning and paraguesia in an otherwise healthy-appearing oral mucosa. Although the etiopathogenesis of Burning Mouth Syndrome is unknown, some studies provide evidence of subclinical inflammation leading to disrupted cytokine levels. To investigate the expression of cytokines and role in the etiopathogenesis of Burning Mouth Syndrome. Online databases (MEDLINE and EMBASE) were searched from November 1986 to November 2018 for case control/cross-sectional studies comparing the levels of cytokines in patients with Burning Mouth Syndrome and healthy controls. A total of eight studies were included in the current review. Four studies were of high and four studies were of moderate quality. Seven studies evaluated IL-6, out of which four showed comparable results, two showed higher levels and one study reported lower levels in Burning Mouth Syndrome patients compared to controls. Four studies assessed IL-2, out of which two reported comparable results whereas one study reported higher levels and one study reported lower levels in Burning Mouth Syndrome patients compared to controls. IL-10 levels were measured in three studies that reported no significant differences in the levels between Burning Mouth Syndrome and healthy controls. The etiopathogenesis of Burning Mouth Syndrome is multifactorial. Studies have provided scientific evidence that inflammation plays a key role in Burning Mouth Syndrome pathogenesis. However, whether up-regulation or down-regulation of specific cytokines contribute to the etiopathogenesis of Burning Mouth Syndrome remains debatable. Further high-quality studies with larger sample size and assessing a wider array of cytokines are warranted in order to obtain strong conclusions.

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.

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

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. 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. 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. 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.

Zespół pieczenia w jamie ustnej (bourning mouth syndrome) - koncepcje patogenetyczne i terapeutyczne.

Burning mouth syndrome (BMS) is a chronic pain condition characterized by pain, burning sensations and dryness within an oral mucosa, without any clinical changes of the latter. It occurs approximately seven times more frequently in women, mostly in perimenopausal age. The psychiatric aspect of BMS is significant: the most frequent co-morbidities are depression and anxiety disorders, and a number of psychotropic drugs play an essential role in its treatment. In the present review, the most important pathogenic and treatment concepts of BMS have been discussed. The BMS may be similar to neuropathic pain and has some related pathogenic elements with fibromyalgia and the restless leg syndrome. In primary BMS, the features of presynaptic dysfunction of dopaminergic neurons and deficiency of endogenous dopamine levels have been demonstrated. Other neurotransmitters such as serotonin, noradrenaline, histamine as well as hormonal and inflammatory factors may also play a role in the pathogenesis of BMS. In the pharmacological treatment of BMS a variety of drugs have been used including benzodiazepines, anticonvulsants, antidepressants and atypical antipsychotic drugs. In the final part of the paper, the possibility of using atypical antipsychotic drug, olanzapine, in the treatment of BMS has been discussed. In the context of the recent studies on this topic, a case of female patient with the BMS lasting more than ten years has been mentioned, in whom the treatment with olanzapine brought about a rapid and significant reduction of symptoms. The probable mechanism of the therapeutic effect of olanzapine in BMS can include its effect on dopaminergic receptors and probably also on histaminergic, noradrenergic and serotonergic ones.

Epithelial expression of vanilloid and cannabinoid receptors: a potential role in burning mouth syndrome pathogenesis.

Burning mouth syndrome (BMS) is an intra-oral burning sensation for which presently no medical or dental causes have been found, and in which the oral mucosa appears normal. It remains an unknown disease for which there is still no long-term treatment. The aim of this study was to assess the epithelial alteration of transient receptor potential vanilloid channel type 1 (TRPV1) and cannabinoid receptors type 1 (CB1) and type 2 (CB2) in the human tongue. The study was performed on eight healthy controls and eight BMS patients. All patients underwent a 3-mm punch biopsy at the anterolateral aspect of the tongue close to the tip. TRPV1, CB1 and CB2 immuno-histochemistry was carried out showing an altered expression of all receptors. In BMS patients there was increased TRPV1, decreased CB1 and increased CB2 expression in tongue epithelial cells also associated with a change in their distribution. It would appear that these receptors are related to BMS. These data could be useful for future characterization of BMS epithelial markers and therapy.

Anxiety, Depression, and Pain in Burning Mouth Syndrome: First Chicken or Egg?

Burning mouth syndrome (BMS) is an idiopathic and chronic pain condition for which patients may experience high levels of pain, anxiety, and depression. So far, it has not yet been well investigated whether specific psychiatric features (anxious traits, personality disorder, or somatization) may play a role in the BMS pathogenesis or whether some BMS symptoms, or BMS itself, may cause secondary psychiatric symptoms. The aim of this study was to evaluate the relationship between pain, depression, and anxiety in BMS and healthy patients in order to hypothesize a possible underlying pathogenetic model. Fifty-three patients with BMS and 51 healthy volunteers matched for sex and age were enrolled. All patients underwent a physical examination, laboratory screening tests, and psychiatric assessment with the following instruments: Visual Analog Scale, the Hamilton Rating Scale for Depression, the State-Trait Anxiety Inventory Form Y 1-2 (STAI Y1-Y2), and the Symptom Checklist-90-Revised (SCL-90-R). BMS patients and healthy volunteers showed a statistically significant difference in psychiatric features: Regression analysis showed that pain is affected by depression (R = 0.373; R(2) corrected = 0.123; F = 8.563; P < .005), and depression is affected by anxiety (R = 0.512; R(2) corrected = 0.248; F = 18.519; P < .001). BMS patients have statistically significant higher scores of anxiety (STAI Y1, P = .026 and STAI Y2, P = .046) and depression (P < .001), and higher SCL-90-R scores on somatization (P = .036) and hostility dimensions (P = .028) than the control group. We may hypothesize that anxiety could determine a secondary demoralization in BMS patients (depression) and depressive symptoms could contribute to pain, accordingly. Therefore, pain could be a somatic feature of depression. Our findings provide an example of a possible pathogenetic model for BMS.

Burning Mouth Syndrome Responsive to Duloxetine: (A Case Report) (P07.273)

Objective: Burning Mouth Syndrome (BMS) or Glossodynia (also known as “Burning tongue” and “Orodynia”) is a condition characterized by a burning or tingling sensation on the lips, tongue, or entire mouth. It is typically a chronic, idiopathic, intraoral mucosal pain condition in the absence of specific oral lesions and systemic disease. CASE : I would like to report a case of a 60-year-old woman in good health with history of insomnia for 2 years taking only Zolpidem (Ambien) 10 mg at night and Paroxetine 37.5 mg daily at home. She stopped taking Paroxetine (Paxil) abruptly 1.5 years earlier for empirical treatment of depression. Since this time, she complained of her tongue being ripped and her mouth feeling that it is “on fire.” She was given a clinical diagnosis of Burning Mouth Syndrome with Sjogren9s syndrome in the differential. She was started on Duloxetine (Cymbalta) 60 mg po daily, resulting in a complete remission of her symptoms including clinical depression. Her burning mouth resolved after 1 week of starting Duloxetine 30 mg po daily and her clinical depression resolved after 4 weeks of taking Duloxetine 60 mg po daily. Her quality of life and level of functioning went back to her baseline. Background The exact pathogenesis of BMS is not clear. Possible causes include nutritional deficiencies, chronic anxiety or depression, type 2 diabetes, menopause, oral disorders such as thrush or dry mouth, or an underlying neuropathic mechanism. It is possible that there is a dysfunction in the trigeminal nociceptive pathways at the level of the peripheral and/or central nervous system. Conclusions: Duloxetine might be a useful and effective treatment of BMS in addition to its other uses with Major Depression, Diabetic Neuropathy, Generalized Anxiety Disorder, Fibromyalgia, and Chronic Musculoskeletal Pain. Disclosure: Dr. Guterman has nothing to disclose.

Burning Mouth Syndrome Responsive to Duloxetine: A Case Report: Table 1

Burning mouth syndrome (BMS) is a chronic, idiopathic, intraoral mucosal pain condition in the absence of specific oral lesions and systemic disease. Among evidence-based pharmacological treatments for this disorder, topical and systemic clonazepam, levosulpiride, selective serotonin reuptake inhibitors have been used with partial results. We report a case of a 65-year-old otherwise healthy woman with a 3-year history of oral burning. Clinical and laboratory evaluations allowed us to make a diagnosis of burning mouth syndrome. She was treated with duloxetine (60 mg p.o. qd), a selective serotonin, and norepinephrine reuptake inhibitor, obtaining a complete remission of symptoms, evaluated via standardized clinical rating scales, and an improvement of her quality of life and level of functioning. The pathogenesis of BMS still remains unclear. Recently, it has been suggested an underlying neuropathic mechanism, demonstrating a dysfunction in the trigeminal nociceptive pathways at peripheral and/or central nervous system level. The rationale behind the administration of duloxetine resides in its central mechanism of action, and analgesic effects previously demonstrated in diabetic peripheral neuropathy, and fibromyalgia. Also, it has been shown to reduce painful physical symptoms associated with depression. We hypothesize that duloxetine might represent a useful, effective, and additional therapeutic option in the treatment of BMS.

Epithelial expression of vanilloid and cannabinoid receptors: a potential role in burning mouth syndrome pathogenesis

Burning mouth syndrome is an intraoral burning sensation in which the oral mucosa has a normal appearance and no medical or dental causes can be found. It remains an unknown disease for which long-term treatment is still lacking. The aim of this study is to assess in epithelial human tongue the expression of three receptors involved in pain transmission, such as a transient receptor potential vanilloid receptor type 1 (TRPV1) which mediates the sensation produced by chilli peppers, cannabinoid receptors type 1 (CB1) and type 2 (CB2), which are pathway-related to TRPV1. Epithelial cells express TRPV1, CB1 and CB2 receptors suggesting a role for these cells in sensory transduction. The study was performed on 8 healthy and 9 BMS patients. All patients underwent a 3-mm punch biopsy at the anterolateral aspect of the tongue close to the tip. Specimens were included in paraffin and serially cut to obtain 6um thick sections. The sections were processed for TRPV1, CB1 and CB2 immunohistochemistry. The analysis showed an altered expression of the studied receptors. In particular we observed an increase of TRPV1, a decrease of CB1 and an increase of CB2 expression in epithelial cells of the tongue with a change in morphological localization. So, these receptors seem to be correlated with BMS. These data could be useful for future characterization of BMS markers and specific therapies.

A prospective, randomized study on the efficacy of tongue protector in patients with burning mouth syndrome

To apply a tongue protector with habit-modifying therapy through self-control, in the patients with burning mouth syndrome (BMS). A prospective, randomized study was made of 65 consecutive patients with BMS. Fifty subjects were randomized to two groups: group A (informed) and group B (informed and the application of a tongue protector). The symptoms were evaluated by VAS, whereas the psychological profile was assessed using the HAD, with application of the quality of life questionnaires SF-36 and OHIP-49. The duration of treatment was 2 months. Fifty patients (46 females and 4 males) completed the study. The VAS scores in group B were 8.2 at baseline and 4.5 after 2 months. The respective scores in group A were 7.1 and 5.6 - the differences between the two groups being significant (P < 0.001). In group B the OHIP-49 yielded lower scores for most of the scales, with significant differences vs group A. In group B the SF 36 yielded significant differences vs group A in physical role, bodily pain, general health and emotional role. Parafunctional traumatism of the tongue should be taken into account in the pathogenesis of BMS with a view to exploring new therapeutic options.

Zinc deficiency may be a cause of burning mouth syndrome as zinc replacement therapy has therapeutic effects

Zinc is known to play an important role for growth and development, the immune response, neurological function, and reproduction. Although the etiology of burning mouth syndrome (BMS) is unknown, zinc deficiency may be implicated in the pathogenesis of BMS. The aim of this study was to demonstrate a causal relationship between zinc deficiency and BMS and to assess whether zinc replacement is an effective therapy for BMS. Serum zinc level was evaluated in 276 patients with BMS. To assess the therapeutic effect of zinc replacement, patients with zinc deficiency were administered a zinc supplement (14.1 mg/day). Pain intensity 6 months after zinc replacement was evaluated using an 11-point numerical scale. We also developed an animal model of zinc deficiency to assess the effects of zinc deficiency on the oral mucosa. Of the 276 patients with BMS, 74 (26.8%) had low serum zinc levels. Zinc replacement therapy lowered the mean numerical pain scale in these patients from 8.1 to 4.1, compared with a mean decrease from 7.7 to 6.7 in a control group (P = 0.004). In our animal model of zinc deficiency, the main pathologic findings were hyperkeratinization and increased mitosis on the dorsum of the tongue, although there were no gross oral mucosal lesions. Zinc deficiency might play a role in some patients with BMS. In such patients, appropriate zinc replacement therapy is effective in relieving symptoms.

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

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. 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. 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. 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.

Calcitonin gene‐related peptide levels in saliva of patients with burning mouth syndrome

Burning mouth syndrome (BMS) is an intraoral burning sensation for which no medical or dental cause can be found. Recent studies suggest that primary neuropathic dysfunction might be involved in the pathogenesis of BMS. Calcitonin gene-related peptide (CGRP) plays an important role in the development of pain and serves as a biological marker of trigeminovascular activation. The aim of this study was to determine the levels of CGRP in the saliva of BMS patients and estimate the trigeminovascular activation in BMS. CGRP levels were measured, by RIA method in 78 BMS patients and 16 healthy subjects. The levels of CGRP were non-significantly decreased in BMS patients in comparison to healthy subjects. These results suggest that trigeminal nerve degeneration may be the underlying cause of BMS.