Search Results (66)

Background/Objectives: Burning Mouth Syndrome (BMS) is a common oral condition in older women and is characterized by a multifactorial etiology. To date, no standardized treatment strategy has been established. The aim of this study was to evaluate the effectiveness of topical application of capsaicin (0.025 mg/cm²) in the form of a mucoadhesive bilayer polymer reducing burning sensations in BMS. The study assessed levels of depression, sleep disturbances, and quality of life. Material and Methods: The proof-of-concept study included 29 patients with symptoms of BMS. The peripheral origin of BMS was confirmed by lingual nerve block. Pain intensity was assessed using the Numeric Rating Scale (NRS-11) and the Short-Form McGill Pain Questionnaire (SF-MPQ). Depression, sleep disturbances, and quality of life were evaluated using the Beck Depression Inventory (BDI), Athens Insomnia Scale (AIS), and WHO Quality of Life Questionnaire (WHOQoL). Results: A reduction in pain was observed in over 86% patients. Decrease in burning at treatment sites was recorded immediately after treatment and also at the 3-month follow-up. Gender, taste disturbances, depression, and age were found to have a significant effect on final NRS-11 scores. Conclusions: Significant reduction in pain intensity was achieved in nearly all treated patients, with adverse effects being rare. Full article

Background: Burning Mouth Syndrome (BMS) is a nociplastic pain condition characterized by altered central nervous system pain processing, significantly impacting patient quality of life. Pharmacological management often involves amitriptyline (monotherapy) and aripiprazole (for refractory cases) in Japan. However, the therapeutic efficacy of these drugs in BMS frequently exhibits a non-sigmoid (U-shaped or bell-shaped) dose–response relationship, indicating a clinically effective dose that is often considerably lower than those used for their primary indications and challenging conventional pharmacological assumptions. Method: This paper synthesizes existing pharmacological knowledge to elucidate the mechanisms underlying the non-dose-dependent actions of amitriptyline and aripiprazole in BMS. It focuses on their specific interactions with key neurotransmitter systems and receptors, particularly N-methyl-D-aspartate (NMDA) receptors and dopamine D2 receptors, to explain the observed non-linear dose–response and the importance of identifying a personalized therapeutic window. Result: Amitriptyline demonstrates efficacy in BMS at low doses (e.g., 25 mg), primarily through its action as an NMDA receptor antagonist via calcium-dependent desensitization and open-channel block, addressing central sensitization. Its effects are distinct from its antidepressant actions, and the “serotonin paradox” highlights the complexity of serotonin’s role in pain. Aripiprazole, utilized for refractory BMS, acts as a dopamine D2 receptor partial agonist, leading to a non-linear dose–response where sustained therapeutic effect is observed at specific low doses (e.g., 1.7–1.8 mg/day). This non-linearity is attributed to partial agonism, alongside interactions with serotonin 5-HT1A and 5-HT2A receptors. The general non-dose-dependency for both drugs is further explained by phenomena such as multiple binding sites with differing affinities, receptor desensitization/downregulation, activation of counter-regulatory mechanisms, and hormesis. Discussion: The observed non-linear dose–response curves for amitriptyline and aripiprazole in BMS underscore the inadequacy of a “one-size-fits-all” treatment approach. This necessitates a shift towards personalized medicine, which considers individual patient factors including pharmacogenomics, comorbidities, age, organ function, and psychological/social profiles. The true “personalized therapeutic window” is a balance between achieving significant pain relief and minimizing adverse effects, emphasizing careful titration and patient-centered care. Conclusions: The pharmacological actions of amitriptyline and aripiprazole in BMS are not linearly dose-dependent, but rather exhibit a personalized therapeutic window driven by complex interactions with NMDA and D2 receptors and adaptive physiological responses. This intricate pharmacological landscape mandates a personalized medicine approach to optimize treatment outcomes, improve patient adherence, and enhance the quality of life for individuals suffering from this challenging nociplastic pain condition. Full article

Tyrosine kinase inhibitors (TKIs), either as single agents or in combination with other drugs, have become a gold standard in many oncological pathologies. The identification, analysis, and clinical management of their multiple and various systemic adverse events are a clear requirement and represent a true challenge in daily practice. For this narrative review, registration clinical trials that have led to the approval of certain TKI protocols in the setting of renal cell carcinoma (RCC) were identified via the latest version of the National Comprehensive Cancer Network (NCCN) kidney cancer guidelines. The following keywords were used: Axitinib, Cabozantinib, Lenvatinib, Pazopanib, Sorafenib, Sunitinib, and Tivozanib. RCC therapies have been proven to frequently induce oral symptoms and pathologies such as stomatitis, dysgeusia, xerostomia, osteonecrosis of the jaws, oral dysesthesia, geographic tongue, and dental and periodontal damage. The aim of this review is to emphasize the mechanisms of these common drug-induced buccodental toxicities associated with TKI therapies in RCC and to draft a general clinical management of these adverse events, in order to improve patients’ quality of life and treatment adherence. Full article

Burning Mouth Syndrome (BMS) presents diagnostic and therapeutic challenges due to its unclear etiology and complex symptomatology. This study, part of a doctoral research project, explores diagnostic delay, triggering factors, and psychotropic medication use in BMS patients. By retrospectively analyzing 300 clinical records, the study offers insight into patterns of diagnosis and treatment, with a focus on differences related to age and sex. The findings contribute to a better understanding of BMS and emphasize the need for timely diagnosis, particularly in older adults, to improve patient outcomes. Full article

Background: Medically unexplained oral symptoms/syndromes (MUOS), such as Burning Mouth Syndrome and Persistent Idiopathic Facial Pain, present significant management challenges due to the lack of standardized treatments and high-level evidence. While pharmacotherapy is often employed, real-world data on treatment adherence—a pragmatic proxy for effectiveness and tolerability—remain sparse, especially in Japan. This study aimed to describe the real-world prescribing patterns of antidepressants and dopamine receptor partial agonists (DPAs) for MUOS and retrospectively investigate their association with treatment continuation. Methods: This retrospective observational study analyzed data from patients initiating pharmacotherapy for MUOS at a specialized clinic in Japan (April 2021–March 2023). We used Cox proportional hazards models to evaluate treatment continuation for amitriptyline monotherapy and antidepressant–aripiprazole adjunctive therapy. The primary outcome was the time to discontinuation. Dosage effects were modeled using B-splines to capture nonlinearity. Results: Among 702 MUOS patients who started pharmacotherapy, 493 received amitriptyline as the first prescription, and 108 received aripiprazole as an adjunctive therapy. For amitriptyline monotherapy, a nonlinear relationship was observed between dosage and discontinuation risk, with a relatively lower hazard around 25 mg/day across age groups. In the antidepressant–aripiprazole adjunctive group, the overall hazard ratio for discontinuation was higher (HR = 4.75, p < 0.0005) compared to non-adjunctive therapy, likely due to indication bias reflecting more treatment-resistant cases. However, within the aripiprazole adjunctive group, a U-shaped relationship was identified between maximum aripiprazole dosage and discontinuation risk, with the lowest hazard (HR ≈ 0.30) observed at approximately 1.7–1.8 mg/day. Mild side effects such as drowsiness, dry mouth, constipation, tremor, insomnia, and weight gain were noted, but no severe adverse events occurred. Conclusions: This real-world data analysis suggests specific dosage ranges (amitriptyline ≈ 25 mg/day; aripiprazole augmentation ≈ 1.7–1.8 mg/day) are associated with longer treatment continuation in MUOS patients. Treatment continuation reflects a crucial balance between symptom relief and tolerability, essential for managing these chronic conditions. It is critical to emphasize that these findings are descriptive and observational, derived from a specialized setting, and do not constitute prescriptive recommendations. They highlight the importance of individualized dosing. Definitive evidence-based strategies require validation through prospective randomized controlled trials. Full article

Burning mouth syndrome (BMS) and oral lichen planus (OLP) are two chronic oral diseases/disorders that continue to pose a challenge for conventional diagnosis and treatment. Both diseases do not occur in isolation but rather appear to reflect a broader interplay of psychological, neurological, endocrine, and immunological factors, i.e., complex disorders in interconnected biological and psychological systems. In BMS, patients often suffer from persistent burning sensations without visible lesions, which may be related to altered pain processing, emotional stress, and dysregulation in the brain regions responsible for interoception and perception. Although OLP is primarily characterised by immune-mediated mucosal damage, it often has significant psychological comorbidity, particularly in the erosive form. Common features such as cortisol imbalance, disturbed cytokine patterns, and high levels of anxiety and depression suggest that these conditions may be due to overlapping systemic disorders. It is no longer sufficient to focus only on the visible lesions or symptom relief. Understanding these diseases/disorders through a more comprehensive psychoneuroendocrine immune system (PNEI) opens up new opportunities for early intervention, improved diagnostics, and more personalised therapeutic strategies that go beyond treating symptoms. Ultimately, these diseases/disorders require a more integrated and patient-centred approach, where understanding the whole system is as important as treating its individual parts. Full article

Background/Objectives: Burning Mouth Syndrome (BMS) is a chronic orofacial pain disorder characterized by persistent intraoral burning sensations without visible mucosal lesions. Although its biopsychosocial complexity is increasingly recognized, cross-cultural comparison data remain limited. Methods: This cross-sectional study assessed 60 patients with BMS (30 Italian, 30 Romanian) who underwent standardized clinical, psychological, and sleep evaluations. Data collected included sociodemographics, clinical characteristics, diagnostic history, comorbidities, and symptomatology. The assessment tools used included the Numeric Rating Scale (NRS), Short Form of the McGill Pain Questionnaire (SF-MPQ), Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HAM-D), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS). Statistical comparisons were conducted using Mann–Whitney U and Fisher’s exact tests with Bonferroni correction. Results: No significant differences were observed in age, sex, or body mass index. Italian patients had fewer years of education (p = 0.001), higher pain intensity (NRS, p < 0.001), poorer sleep quality (PSQI, ESS, p = 0.001), and more frequent pre-existing sleep disorders (p < 0.001). Romanian patients showed higher levels of anxiety (HAM-A, p < 0.001), longer diagnostic delays (p = 0.002), and more dysesthetic or perceptual symptoms, including tingling and oral dysmorphism (p < 0.05). Stressful events before onset were more common among Romanians (p < 0.001), while Italians more often received a correct diagnosis at first consultation (p = 0.005). Conclusions: This first cross-national comparison of BMS in Western and Eastern Europe shows that cultural, healthcare, and clinician education differences can shape symptom profiles, comorbidities, and diagnostic delays, underscoring the need for personalized, country-specific management strategies. Full article

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

Objectives: Burning mouth syndrome (BMS) is a chronic, painful, idiopathic condition of the oral cavity, characterized by the absence of visible pathological changes on the oral mucosa and normal laboratory findings. Recent evidence from the literature supports the classification of BMS as a neuropathic condition. It has been proposed that oxidative stress may contribute to neuropathic pain. N-acetylcysteine (NAC) is an antioxidant that exhibits neuroprotective properties. The aim of the study was to evaluate the efficacy of N-acetyl cysteine in the treatment of burning mouth syndrome (BMS). Methods: Eighty female patients with previously diagnosed BMS were randomly assigned to one out of two groups. One group received N-acetyl cysteine (600 mg/twice a day) and the other received placebo, for an eight-week period. The outcome was measured by the Oral Health Impact Profile-14 (OHIP-14) quality of life questionnaire and Numeric Pain Rating Scale, for burning and discomfort, both before and after completing the therapy. Results: Both groups experienced a significant reduction in burning and discomfort sensations, along with a significant improvement in oral health-related quality of life. However, the difference between the treatment and control group was not statistically significant. Conclusions: NAC does not significantly improve the oral health-related quality of life, burning sensations, and discomfort in BMS subjects compared to placebo. Full article

Objective: Burning mouth syndrome (BMS) is a chronic and often debilitating orofacial pain condition characterized by a burning sensation in the oral mucosa without clear abnormal lesions. While its etiology is considered multifactorial, the underlying pathophysiology remains unclear. This narrative review aims to synthesize existing functional magnetic resonance imaging (fMRI) studies to shed light on the central neural mechanisms contributing to BMS. Methods: A focused electronic search was conducted across the PubMed and J-STAGE databases for relevant articles published in English from January 2000 to May 2025. The review prioritized studies investigating brain structure and function using fMRI in individuals with BMS. Results: Our synthesis of the literature consistently demonstrated that the brains of individuals with BMS exhibit augmented connectivity within the medial pain system and a diminished gray matter volume in the medial prefrontal cortex (mPFC). These findings suggest a crucial role for altered brain circuitry, particularly a reduction in the output of the basal ganglia dopamine system, in the experience of BMS pain. Conclusions: The consistent fMRI findings strongly indicate that BMS involves significant functional and structural brain alterations. The observed changes in the mPFC and its connections to the basal ganglia dopamine system highlight this pathway as a potential target for both pharmacological and non-pharmacological neurological interventions for individuals with BMS. 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

Background/Objectives: The potential influence of lycopene on mental health was indicated in some studies, but it was not summarized within any systematic review so far. The aim of the presented study was to analyze the influence of lycopene on mental health within a systematic review of Randomized Controlled Trials (RCTs). Methods: The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and it was based on PubMed, Web of Science, Cochrane, and Google Scholar databases, while the RCTs published until February 2025 were included. The systematic review was registered within the database of the International Prospective Register of Systematic Reviews (PROSPERO) (CRD420250650525). The studies were considered where the adult population was studied; intervention was based on oral lycopene intake in any form (lycopene supplement, lycopene-enriched functional food, or regular food product being an important source of lycopene); lycopene intake of a specified dose was applied; any mental health result was studied using a valid psychological measure. After duplicate removal, 642 studies were screened, and finally, six RCTs were included and assessed using the revised Cochrane risk-of-bias tool for randomized trials, while various mental health outcomes were allowed (excluding subjects with intellectual disabilities, eating disorders, and neurological disorders). Each stage of screening, inclusion, reporting, and assessment was conducted independently by two researchers. Results: The included studies were conducted in populations of healthy individuals (one study), but mainly in individuals with various diseases: Benign Prostatic Hyperplasia (BPH) (two studies), Burning Mouth Syndrome (BMS) (one study), xerostomia (one study), and infertility (one study). Within the included studies, various lycopene sources were applied, including lycopene supplements, functional foods, and regular food products, as well as various lycopene doses from 1.35 mg to 27.8 mg per day. The included studies assessed quality of life (five studies), depression and anxiety (two studies), stress (two studies), and mood states (one study). In spite of the fact that all six included studies were RCTs, the comparison between the intervention group and placebo group was made in only four studies, and none of them stated the difference between the compared groups. A low risk of bias was concluded for three studies (all of them not confirming the influence of lycopene on mental health), and a high risk of bias was found in three studies (one of them not confirming, and two not conclusive). Conclusions: The evidence gathered within the systematic review of RCTs did not confirm any influence of lycopene on mental health. Further RCTs are needed to verify the influence of lycopene provided within supplements, functional foods, and regular food products on various mental health problems in diverse populations. Full article

Background/Objectives: Burning mouth syndrome (BMS) is a chronic pain disorder of the oral cavity in the absence of organic disease and is prevalent among menopausal women. Estrogen may be involved in the formation of nerves involved in pain. Methods: This paper presents an inferred mechanism for the relationship between estrogen and BMS based on a synthesis and interpretation of findings from a selection of published studies. Results: Estrogen influences the formation of neural circuits in BMS by dividing the complex pain circuit into the following three components: the peripheral pain circuit, brain network pain circuit, and memorized pain circuit. Conclusions: The development of BMS may be influenced by the formation of neural circuits by sex hormones. Full article

The objective of the study was to determine the relationship between burning, xerostomia, dysgeusia and other subjective symptoms in patients with burning mouth syndrome (BMS). This cross-sectional study was conducted at the Dental Polyclinic Split, Split, Croatia. A total of 71 patients with BMS, i.e., 60 women and 11 men, were included in the study. The patients were divided into four subgroups: burning (B), burning and xerostomia (BX), burning and dysgeusia (BD), burning, xerostomia and dysgeusia (BXD). The following data were collected from all patients: sociodemographic status, comorbidities, medications, characteristics of the burning, presence of other subjective symptoms, topography of the burning. The majority of patients with BMS were women (86.0%) with an average age of about 65 years. Gastrointestinal diseases were the most common comorbidity (48.35%), and the most commonly used medications were proton pump inhibitors (PPIs) (29.8%). In the largest number of patients (N = 34), the burning symptom worsened in the evening hours (p = 0.059). The majority of BMS patients suffered from burning symptoms that occurred continuously (N = 54, 75.13%) and from an improvement (reduction/cessation) of symptoms during meals (N = 54, 76.65%). Of the other subjective symptoms, changes in the morphology of the tongue (10.6%) and a feeling of swelling (9.1%) were the most common. The tongue was the most common localization (67.35%). The multivariable logistic regression analysis showed a statistically significant effect of female gender (p = 0.049) as a potential positive predictor in subgroup B. The sociodemographic and medical data collected cannot explain the different occurrence of symptoms in the four subgroups of patients with BMS. Full article

Peppers (Capsicum spp.) represent not only a plant with a demonstrated history of diverse medicinal applications but also a species having non-neglectable adverse effects potential. “Chili burn” or Hunan hand syndrome represents a type of contact dermatitis rarely appearing after using chili peppers. Here, a case of “chili burn” with no specific treatments or sequelae is presented. A young woman presented with contact dermatitis after first- and second-time dermal exposure to a chili pepper. A strong burning sensation appeared shortly after on the hands and around the mouth after exposure to the plant. The patient applied non-specific measures (hand washing with mild soap and rinsing the affected areas with acidic solutions) with minor improvement; finally, the “chili burn” resolved itself. No other medicines were applied, and no consequences were recorded. Although rare, the use of chili pepper has the potential to cause contact dermatitis. The awareness of medical professionals of this entity should provide adequate diagnosis and treatment for patients. Full article