Search Results (11)

Background: Chronic primary orofacial pain (COFP) affects approximately 7% of the population and often leads to reduced quality of life. Patients frequently undergo multiple assessments and treatments across healthcare disciplines, often without a definitive diagnosis. The 2019 ICD-11 classification of chronic primary pain clusters together COFP subtypes based on chronicity and associated functional and emotional impairment. Objective: This study aimed to evaluate whether these subtypes of COFP share common underlying mechanisms by comparing neuroimaging findings. Methods: A systematic review was conducted in accordance with PRISMA guidelines. Searches were performed using Medline (OVID) and Scopus up to April 2025. Inclusion criteria focused on MRI-based neuroimaging studies of participants diagnosed with COFP subtypes. Data extraction included participant demographics, imaging modality, brain regions affected, and pain assessment tools. Quality assessment used a modified Coleman methodological score. Results: Fourteen studies met the inclusion criteria, all utilising MRI and including two COFP subtypes (temporomandibular disorder and burning mouth syndrome). Resting- and task-state imaging revealed overlapping alterations in several brain regions, including the thalamus, somatosensory cortices (S1, S2), cingulate cortex, insula, prefrontal cortex, basal ganglia, medial temporal lobe, and primary motor area. These changes were consistent across both TMD and BMS populations. Conclusions: The findings suggest that chronic primary orofacial pain conditions (TMD and BMS) may share common central neuroplastic changes, supporting the hypothesis of a unified pathophysiological mechanism. This has implications for improving diagnosis and treatment strategies, potentially leading to more targeted and effective care for these patients. Full article

Objective:Burning mouth syndrome (BMS) is a chronic, intractable orofacial pain condition characterized by a burning sensation in the oral mucosa without discernible lesions. The syndrome predominantly affects menopausal and postmenopausal women and is considered a form of nociplastic pain, where the processing of pain stimuli is altered. Given the significant sex disparity, it is crucial to consider underlying neurobiological differences that may inform treatment. This review explores potential pharmacological targets by examining the pathological mechanisms of BMS. Method of Research: A narrative review approach was utilized to systematically explore and synthesize literature regarding the pathophysiology of BMS and to identify receptors implicated in the enhancement of sensory transmission and the altered processing of pain stimuli. Results: The mechanism of enhanced sensory transmission points to receptors such as TRPV1, P2X3, and CB2 as potential targets. However, considering the nociplastic nature of BMS and its prevalence in women, mechanisms involving altered central pain processing are paramount. Research indicates significant sex differences in glutamate transmission and plasticity within reward-related brain regions. This suggests that the N-methyl-D-aspartate (NMDA) receptor, a cornerstone of glutamate signaling and synaptic plasticity, is a primary therapeutic target. Furthermore, the altered processing of pain and reward, which is a key feature of chronic pain, implicates the brain’s dopaminergic system. A decrease in dopamine D2 receptor function within this system is believed to contribute to the pathology of BMS. Estrogen receptors are also considered relevant due to the menopausal onset. Conclusions: Based on the evidence, the most promising targets for pharmacotherapy in BMS are likely the NMDA receptor and the dopamine D2 receptor. The high prevalence of BMS in women, coupled with known sex differences in the glutamate and dopamine pathways of the reward system, provides a strong rationale for this focus. Effective treatment strategies should therefore aim to modulate these specific systems, directly or indirectly controlling NMDE receptor hyperactivity and addressing the decreased D2 receptor function. Further research into therapies that specifically target this sex-linked neurobiology is essential for developing effective pharmacotherapy for BMS. Full article

The aim of our study was to assess the relationship between the concentration/activity of salivary stress biomarkers (cortisol, α-amylase) and the psychological profile of patients with oral lichen planus (OLP) and primary burning mouth syndrome (BMS). A total of 160 subjects participated in this case–control study: 60 patients with OLP; 60 patients with primary BMS; and 40 control subjects. Unstimulated whole saliva (UWS) was collected between 9 and 10 a.m. Salivary biomarkers were analyzed by enzyme-linked immunosorbent assays (ELISAs). Psychological assessment was evaluated with the Depression, Anxiety, and Stress Scale (DASS-21). The patients with primary BMS had higher salivary cortisol concentrations and α-amylase activity (0.52 vs. 0.44 µg/dL; 160,531 vs. 145,804 U/L; one-way analysis of variance (ANOVA) with post hoc Scheffe test) compared with patients with OLP. The patients with primary BMS had statistically significant higher scores for depression, anxiety, and stress compared with patients with OLP and control subjects (p < 0.001, Kruskal–Wallis test). There was a strong positive correlation between anxiety and depression, stress and depression, and stress and anxiety in patients with OLP and BMS (p < 0.001 and p < 0.001, respectively; Spearman’s correlation). There was a good positive correlation between symptom intensity (pain/burning) and psychological profile (depression, anxiety, stress) in patients with primary BMS (r = 0.373, p = 0.003; r = 0.515, p < 0.001; r = 0.365, p = 0.004, respectively; Spearman’s correlation). This case–control study is the first to compare the psychoendocrinological profile of patients with two different oral diseases. The patients with BMS showed a higher concentration/activity of salivary stress biomarkers (cortisol, α-amylase) and a stronger association with mental disorders compared with patients with OLP. However, an interdisciplinary psychoneuroimmunological approach is equally important in both patient groups (OLP and BMS), regardless of whether mental disorders are the cause or the consequence. Full article

Background: Burning Mouth Syndrome (BMS) is an idiopathic condition mainly affecting middle-aged and older individuals with hormonal disturbances or psychiatric disorders and is characterized by chronic pain. The etiopathogenesis of this multifactorial syndrome is largely unknown. The objective of the present systematic review was therefore to evaluate the relationship of BMS with depressive and anxiety disorders in middle-aged and older individuals. Methods: We selected studies evaluating BMS and depressive and anxiety disorders assessed with validated tools, published from their inception up to April 2023, using PubMed, MEDLINE, EMBASE, Scopus, Ovid, and Google Scholar databases and adhering to the PRISMA 2020 guidelines/PRISMA 2020 27-item checklist. This study is registered on PROSPERO (CRD42023409595). The National Institutes of Health Quality Assessment Toolkits for Observational Cohort and Cross-Sectional Studies were used to examine the risk of bias. Results: Two independent investigators rated 4322 records against the primary endpoint and found 7 records meeting the eligibility requirements. Anxiety disorders were found to be the most common psychiatric disorders related to BMS (63.7%), followed by depressive disorders (36.3%). We found a moderate association of BMS with anxiety disorders, with multiple studies included (n = 7). Moreover, we found a low association of BMS with depressive disorders (included studies, n = 4). The role of pain appeared to be controversial in explaining these associations. Conclusions: In middle-aged and older subjects, anxiety and depressive disorders may be potentially related to the development of BMS. Furthermore, also in these age groups, females showed higher risk of developing BMS than males, even when taking into account multimorbidity such as sleep disorders, personality traits, and biopsychosocial changes as suggested by study-specific findings. Full article

Burning mouth syndrome (BMS) is a chronic disorder characterized by a burning sensation in the oral cavity, often accompanied by xerostomia, with no relevant clinical or laboratory findings. This study aimed to investigate diagnostic values of quantitative parameters of salivary gland scintigraphy for BMS in patients with xerostomia. A total of 164 patients who underwent salivary gland scintigraphy for the workup of xerostomia were retrospectively reviewed. All patients were classified into patient groups with primary BMS, secondary BMS, and non-specific xerostomia. From salivary gland scintigraphy, 22 quantitative parameters were calculated and their diagnostic values were assessed based on the area under the receiver operating characteristic curve (AUC) values. Among salivary gland scintigraphy parameters, uptake speed in the left submandibular gland showed the highest AUC value (0.647) for detecting BMS and pre-stimulatory oral activity showed the highest AUC value (0.710) for detecting primary BMS. A salivary gland scintigraphy scoring system based on these two parameters further enhanced the diagnostic ability, demonstrating AUC values of 0.731 for BMS and 0.782 for primary BMS. These results suggest a potential diagnostic value of the quantitative parameters of salivary gland scintigraphy for detecting BMS in patients with xerostomia. Full article

Neuropathic pain (NP) can be challenging to treat effectively as analgesic pharmacotherapy (MED) can reduce pain, but the majority of patients do not experience complete pain relief. Our pilot approach is to assess the feasibility and efficacy of an evidence-based photobiomodulation (PBM) intervention protocol. This would be as an alternative to paralleled standard analgesic MED for modulating NP intensity-related physical function and quality of life (QoL) prospectively in a mixed neurological primary burning mouth syndrome and oral iatrogenic neuropathy study population (n = 28). The study group assignments and outcome evaluation strategy/location depended on the individual patient preferences and convenience rather than on randomisation. Our prospective parallel study aimed to evaluate the possible pre/post-benefit of PBM and to allow for a first qualitative comparison with MED, various patient-reported outcome measures (PROMs) based on Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT-II) were used for up to a nine-month follow-up period in both intervention groups (PBM and MED). The PBM protocol applied to the PBM group was as follows: λ810 nm, 200 mW, 0.088 cm², 30 s/point, 9 trigger and affected points, twice a week for five consecutive weeks, whereas the MED protocol followed the National Institute of Clinical Excellence (NICE) guidelines. Our results showed that despite the severe and persistent nature of the symptoms of 57.50 ± 47.93 months at baseline in the PBM group, a notably rapid reduction in PIS_max on VAS from 7.6 at baseline (T0) to 3.9 at one-month post-treatment (T3) could be achieved. On the other hand, mean PIS_max was only reduced from 8.2 at baseline to 6.8 at T3 in the MED group. Our positive PBM findings furthermore support more patients’ benefits in improving QoL and functional activities, which were considerably impaired by NP such as: eating, drinking and tasting, whereas the analgesic medication regimens did not. No adverse events were observed in both groups. To the best knowledge of the authors, our study is the first to investigate PBM efficacy as a monotherapy compared to the gold standard analgesic pharmacotherapy. Our positive data proves statistically significant improvements in patient self-reported NP, functionality, psychological profile and QoL at mid- and end-treatment, as well as throughout the follow-up time points (one, three, six and nine months) and sustained up to nine months in the PBM group, compared to the MED group. Our study, for the first time, proves the efficacy and safety of PBM as a potent analgesic in oral NP and as a valid alternative to the gold standard pharmacotherapy approach. Furthermore, we observed long-term pain relief and functional benefits that indicate that PBM modulates NP pathology in a pro-regenerative manner, presumably via antioxidant mechanisms. Full article

Background: The objective of this study was to determine the most effective treatment option for burning mouth syndrome. Methods: Informative treatment alone, B vitamin injections, oral cavity probiotics, and low-level laser therapy were evaluated and compared. The study included new patients diagnosed with burning mouth syndrome, who were randomly allocated into one of four treatment groups. The primary outcome was improvement in patient’s quality of life as determined by a self-perceived Oral Health Impact Profile-14 (OHIP-14) quality of life questionnaire before and after therapy. The secondary outcome was determination of mucosal symptom intensity according to visual analog scale (VAS) grading from 0 to 10. Data were submitted to statistical analysis. Results: A total of 62 patients completed the study. Oral cavity probiotics and LLLT scores for OHIP-14 resulted in a statistically significant difference before and after therapy. Standardized effect sizes between OHIP scores before and after treatment were the greatest for patients who had received oral cavity probiotics. Conclusions: Oral cavity probiotics and LLLT were the most effective treatment for improvement in quality of life. Further investigation on a larger group of patients is required. Full article

Mitochondrial homeostasis is crucial for energy production and neuronal survival in neurological primary burning mouth syndrome (npBMS). Photobiomodulation therapy (PBMT) has been utilised in npBMS management, however, its role of intervention remains controversial. The aim of this systematic review and meta-analysis of CRD 42020198921 PROSPERO registration reference was to oversee and determine the efficacy of PBMT in patients with npBMS, identifying the gaps and bridge them by proposing recommendations for future studies purposes. PRISMA guidelines and Cochrane Collaboration recommendations followed. Various search engines employed to analyse a total of 351 studies of which 12 were included. A wide range of utilised PBM wavelengths was between 635–980 nm and the power output ranged between 30 mW and 4000 mW. A high risk of bias (RoB) was noted in 7 out of 12 included studies (58.3%), as results of qualitative analysis. Meta-analysis findings of 4 out of 12 studies showed statistically significant intergroup differences (SSID) for visual analogue scale (VAS) values (MD = −1.47; 95% CI = −2.40 to −0.53; Z = 3.07 (p = 0.002) whereas meta-analysis on 5 out of 12 studies revealed SSID for anxiety/depression and quality of life (MD = −1.47; 95% CI = −2.40 to −0.53; Z = 3.07 (p = 0.002), favouring PBMT group to the control treatment strategies. Despite the inconsistency and diversity in PBM parameters (wavelength, power, light source, spot size, emission mode, energy per point, total energy) and treatment protocols (exposure time, number of sessions, time interval between sessions, treatment duration)—majority of the included studies showed positive PBM results. The high RoB and meta-analytical heterogeneity in the eligible studies warrant the necessity to perform well-designed and robust RCTs after acknowledging the drawbacks of the available scientific literature and addressing our suggested recommendations highlighted in our review. Full article

The pathophysiology of primary burning mouth syndrome (BMS) has been extensively debated but is poorly understood despite a large number of hypotheses attempting to explain its etiopathogenic mechanisms. The aim of the present work was to systematically review papers that could provide arguments in favour of the neuropathic and psychogenic components of primary BMS for a better understanding of the disease. This systematic review (SR) was registered in PROSPERO (CRD42021224160). The search was limited to articles in English or French from 1990 to 01 December 2020. A total of 113 articles were considered for data extraction. We divided them into four subgroups: pharmacological and nonpharmacological management studies (n = 23); neurophysiological studies (n = 35); biohistopathological studies (n = 25); and questionnaire-based studies (n = 30). Several of these studies have shown neuropathic involvement at various levels of the neuraxis in BMS with the contribution of quantitative sensory testing (QST), functional brain imaging, and biohistopathological or pharmacologic studies. On the other hand, the role of psychological factors in BMS has also been the focus of several studies and has shown a link with psychiatric disorders such as anxiety and/or depression symptoms. Depending on the patient, the neuropathic and psychogenic components may exist simultaneously, with a preponderance of one or the other, or exist individually. These two components cannot be dissociated to define BMS. Consequently, BMS may be considered nociplastic pain. Full article

Objective: This systematic review and meta-analysis of published randomized controlled trials examines a possible relationship between optical spot size at surface tissue, irradiance, radiant exposure, total energy delivered, operator technique and reported clinical outcomes. Background: Clinical photobiomodulation (PBM) therapy has achieved a high level of evidence-based acceptance in the mitigation of oral mucositis associated with cancer radiotherapy and chemotherapy, and supportive clinical research in relation to orthodontic tooth movement, oral medical conditions, including burning mouth syndrome, xerostomia and lichen planus. Inconsistent outcomes have been reported not withstanding a substantial body of primary supportive research from clinical, in vitro and animal studies. Materials and Methods: PubMed, Cochrane Database of Reviews and Google Scholar search engines were applied to identify human clinical trials of PBM therapy in clinical dentistry. A total of 766 articles between February 2009 and June 2020 were identified and following a full text evaluation, 38 papers with sufficient data to permit analyses are included in this investigation. Results: Following a detailed assessment of potential factors that may have an influence in clinical outcome, a clear trend is apparent associating optical spot size to a positive or negative effect. Furthermore, there is a clear difference in the reported results in relation to total energy applied, delivery techniques and optical parameters, which merits further investigation. Factorial statistical analyses identified an association between smaller optical surface applications and an overall lower level of reported clinical success in treating superficial and deeper targets, and correspondingly sub-surface larger target tissues were found to be more responsive to therapy by use of a larger optical surface spot size. Moreover, use of multiple small diameter probe applications was found to provide inconsistent results. Conclusions: Many factors can confound clinical success including variations in anatomy, site location, clinical condition and subject individuality. To achieve higher levels of predictable outcome, a mature appreciation of these factors, plus an expanded understanding of laser parametry, tissue volume and target depth to deliver an adequate dose within current recommended guidelines, is essential. Full article

Senses of smell and taste, saliva flow, and dental status are considered as important factors for the maintenance of a good nutritional status. Salivary secretory rates, chemosensory function, burning mouth sensation, halitosis and dental status were investigated in 58 patients with primary Sjögren’s syndrome (pSS), 22 non-Sjögren’s syndrome sicca (non-SS) patients, and 57 age-matched healthy controls. A significantly greater proportion of patients with pSS and non-SS had ageusia, dysgeusia, burning mouth sensation, and halitosis compared to controls. Patients with pSS had significantly lower olfactory and gustatory scores, and significantly higher caries experience compared to controls. Patients with pSS and non-SS patients had significantly lower unstimulated and stimulated whole saliva secretory rates compared to controls. The findings indicated that several different aspects of oral health were compromised in both, patients with pSS and non-SS, and this may affect their food intake and, hence, their nutritional status. Although non-SS patients do not fulfill Sjögren’s syndrome classification criteria, they have similar or, in some cases, even worse oral complaints than the patients with pSS. Further studies are needed to investigate food preferences, dietary intake, and nutritional status in these two patient groups in relation to their health condition. Full article