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

ABSTRACT: 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.

SUBMITTER: Krief G

PROVIDER: S-EPMC6423135 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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

Krief Guy G Haviv Yaron Y Deutsch Omer O Keshet Naama N Almoznino Galit G Zacks Batia B Palmon Aaron A Aframian Doron J DJ

Scientific reports 20190318 1

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 electr ...[more]

PMID: 30886243

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Project description:Background: Due to its common association with chronic pain experience, cognitive impairment (CI) has never been evaluated in patients with burning mouth syndrome (BMS). The purpose of this study is to assess the prevalence of CI in patients with BMS and to evaluate its relationship with potential predictors such as pain, mood disorders, blood biomarkers, and white matter changes (WMCs). Methods: A case-control study was conducted by enrolling 40 patients with BMS and an equal number of healthy controls matched for age, gender, and education. Neurocognitive assessment [Mini Mental State Examination (MMSE), Digit Cancellation Test (DCT), the Forward and Backward Digit Span task (FDS and BDS), Corsi Block-Tapping Test (CB-TT), Rey Auditory Verbal Learning Test (RAVLT), Copying Geometric Drawings (CGD), Frontal Assessment Battery (FAB), and Trail Making A and B (TMT-A and TMT-B)], psychological assessment [Hamilton Rating Scale for Depression and Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and 36-Item Short Form Health Survey (SF-36)], and pain assessment [Visual Analogic Scale (VAS), Total Pain Rating index (T-PRI), Brief Pain Inventory (BPI), and Pain DETECT Questionnaire (PD-Q)] were performed. In addition, blood biomarkers and MRI of the brain were recorded for the detection of Age-Related WMCs (ARWMCs). Descriptive statistics, the Mann-Whitney U-test, the Pearson Chi-Squared test and Spearman's correlation analysis were used. Results: Patients with BMS had impairments in most cognitive domains compared with controls (p < 0.001**) except in RAVLT and CGD. The HAM-D, HAM-A, PSQI, ESS, SF-36, VAS, T-PRI, BPI and PD-Q scores were statistically different between BMS patients and controls (p < 0.001**) the WMCs frequency and ARWMC scores in the right temporal (RT) and left temporal (LT) lobe were higher in patients with BMS (p = 0.023*). Conclusions: Meanwhile, BMS is associated with a higher decline in cognitive functions, particularly attention, working memory, and executive functions, but other functions such as praxis-constructive skills and verbal memory are preserved. The early identification of CI and associated factors may help clinicians to identify patients at risk of developing time-based neurodegenerative disorders, such as Alzheimer's disease (AD) and vascular dementia (VD), for planning the early, comprehensive, and multidisciplinary assessment and treatment.

Project description:BackgroundThe relationship between hypertension (HTN) and chronic pain is still a matter of debate, and its prevalence in patients with burning mouth syndrome (BMS) has never been evaluated. This study aimed to assess the prevalence of HTN in women with BMS and to evaluate its relationship with potential predictors such as risk factors for cardiovascular diseases, pain, and mental health status analyzing differences with healthy women.MethodsIn total, 250 women with BMS (WBMS) were prospectively recruited and compared with an equal number of healthy women (HW) matched for age. Education, body mass index, smoke and alcohol consumption, intensity and quality of pain, and psychological profile were further investigated to identify the potential predictors of HTN. Specifically, pain assessment [the Numeric Rating Scale (NRS) and Short-Form McGill Pain Questionnaire (SF-MPQ)] and psychological assessment [Hamilton Rating Scale for Depression and Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS)] was carried out for the participants.ResultsHTN was found in 128 (51.2%) WBMS and 76 (30.4%) HW (p < 0.001**). The scores of the NRS, SF-MPQ, HAM-D, HAM-A, and PSQI were statistically significantly higher in the WBMS than in the HW (p < 0.001**). A strongly linear correlation between HTN and employment status, systemic diseases, and education level (p < 0.001**) was found in WBMS, while a strong correlation between HTN and employment status, hypercholesterolemia, systemic diseases, and drug consumption was found in HW (p < 0.001**). No statistically significant correlation was found between HTN and pain, anxiety, depression, and sleep disturbances.ConclusionThese results suggest that WBMS showed a higher prevalence of HTN compared with controls. Unemployed WBMS with lower education and other systemic comorbidities are at an increased risk of developing HTN. HTN is associated with alteration in the vascular structure and function of the brain, and these processes accelerate brain aging, which contributes to a reduction in intracortical connectivity, thus affecting the modulatory system of control of pain in patients with BMS, independently of their mental health assessment. Predictors that may underlie this association remain unclear, taking into account the differences found in HW, and should be further elucidated.

Project description:Background and Objectives: Burning mouth syndrome (BMS) is a state in which a patient experiences intraoral burning or a dysesthetic sensation without clinically evident causative lesions in the oropharyngeal area. The disorder is linked to a variety of conditions, including dry mouth, Candida, and bacterial infections. The aim of this study was to determine the incidence of oral Candida and/or bacterial infections among patients with BMS and whether they have an effect on pain/burning and salivary flow levels. Objectives: (1) Gather patient data regarding the presence of oral infections, dry mouth, and pain levels in the morning, afternoon, and evening periods; (2) data analysis and assessment to determine medians, means, frequencies, correlations, and statistically significant differences between patient groups. Materials and Methods: Overall, 173 patients (23 males and 150 females) with BMS and 13 controls (five males and eight females) took part in the study. We measured pain/burning levels, unstimulated and stimulated salivary flow, the percentage of patients infected with Candida species and/or bacterial species, and the said species growth in Petri dishes. Results: Candida albicans was the most commonly found infection among patients with BMS (n = 28, 16.2%). Overall, 21.4% patients with BMS were diagnosed with either C. albicans or another Candida species. Enterobacter had the richest growth among patients with BMS (7.5% out of the infected 10.4% BMS patients). No statistical significance could be noted between the existence of either Candida species or bacterial species infections and changes in pain/burning and salivary flow levels. Negative correlations were noted between age and unstimulated and stimulated salivary flow, and positive correlations were noted between age and Candida andspecific bacteria species' growth levels. Conclusions: Although patients with present bacterial or Candida infections showed a marginal increase in pain/burning levels, no direct statistically significant associations could be made between the presence of Candida species or other bacteria and the symptoms among patients with BMS.

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

Publications

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

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