Therapeutic effects of clonazepam in patients with burning mouth syndrome and various symptoms or psychological conditions.

Burning mouth syndrome (BMS) is frequently accompanied by dysgeusia and xerostomia. Clonazepam has been widely prescribed and is effective, but it is unclear whether clonazepam also affects the symptoms that accompany BMS, or whether such symptoms affect treatment outcomes. Here, we investigated the therapeutic outcomes in BMS patients with various symptoms or comorbidities. We retrospectively reviewed 41 patients diagnosed with BMS between June 2010 and June 2021 at a single institution. Patients were instructed to take clonazepam for 6 weeks. Before the first dose, burning pain intensity was measured using a visual analog scale (VAS); the unstimulated salivary flow rate (USFR), psychologic characteristics, site(s) of pain, and any taste disturbance were evaluated. Burning pain intensity was measured again after 6 weeks. Thirty-one of the 41 patents (75.7%) exhibited a depressed mood, whereas more than 67.8% of the patients exhibited anxiety. Subjective xerostomia was reported by ten patients (24.3%). The mean salivary flow rate was 0.69 mL/min and hyposalivation (an unstimulated salivary flow rate ≤ 0.5 mL/min) was apparent in ten patients (24.3%). Dysgeusia was present in 20 patients (48.7%); a bitter taste (n = 15, 75%) was reported by the largest proportion of patients. Patients who reported a bitter taste responded best in terms of burning pain reduction after 6 weeks (n = 4, 26.6%). Overall, 32 patients (78%) reported decreased oral burning pain after clonazepam (mean VAS score changed from 6.56 to 5.34) use. Patients who reported taste disturbances exhibited a significantly greater decrease in burning pain, compared with other patients (mean VAS score changed from 6.41 to 4.58) (p = 0.02). Clonazepam significantly improved burning pain in BMS patients who had taste disturbances.

Evaluation of peripheral nerve fibers and mast cells in burning mouth syndrome.

Emerging evidence has revealed a cross-talk in the etiopathogenesis of burning mouth syndrome (BMS) related to peripheral nerve fibers (NF) and neuropeptides secreted by mast cells. Here, we investigated the S-100+ density and PGP 9.5+ integrity of peripheral NF and the tryptase+ mast cell density in the oral mucosa of BMS patients and healthy individuals. A total of 23 oral mucosa specimens (12 BMS and 11 controls) were evaluated. The clinical diagnosis of BMS was based on a careful examination, excluding other local and systemic causes. Samples were taken from an incisional biopsy of the tongue mucosa of individuals with symptomatic BMS, while the margins of the non-neoplastic tongue biopsy served as controls of healthy individuals. Immunohistochemistry was performed to determine the density/mm2 of S-100+, PGP 9.5+ peripheral NF, and tryptase+ mast cells. Similar densities of S-100+, PGP 9.5+ peripheral NF, and tryptase+ mast cells were found in cases of BMS, with a median value of 3.70, 0.70, and 29.24/mm2, respectively, and in the control group, with a median value of 2.60, 0.80, and 26.01/mm2, respectively (p > 0.05). Moreover, the relationship between S100+ and PGP 9.5+ peripheral NF was the same in both groups (p = 0.70). This study demonstrated that there were no alterations in the density and integrity of peripheral NF in the tongue of symptomatic BMS patients. However, the sensitization of peripheral NF in this disease may not depend on mast cell density.

Innovative histological and histochemical characterization of tongue biopsies from patients with burning mouth syndrome.

OBJECTIVES: The present pilot study aims to perform an innovative histological and histochemical characterization of samples from patients with burning mouth syndrome (BMS) to correlate these findings with the clinical scenario. METHODS: To carry out this objective, the study samples were stained with the hematoxylin-eosin stain and later, an histochemical study was carried out to determine the composition of the extracellular matrix (ECM) using the stains of Alcian Blue, Picrosirius, Reticulin from Gomori and Verhoeff. RESULTS: The results of this study revealed histological patterns compatible with cellular hypertrophy in different layers of the epithelium as well as a greater keratinization in BMS cases. On the other hand, a lower amount of proteoglycans and a greater amount of collagen fibers were observed compared to the control. In addition, older patients had fewer reticular fibers and younger patients had fewer elastic fibers compared to the control. CONCLUSIONS: In conclusion, the present study shows the existence of a correlation between the histological patterns, age and symptoms of patients with BMS. Therefore, it is necessary to develop synergistic studies in order to assess and implement new classification systems that could improve the therapeutic approach of patients with BMS.

Low-dose naltrexone for treatment of burning mouth syndrome.

OBJECTIVE: The International Classification of Disease defines burning mouth syndrome (BMS) as a chronic intraoral burning sensation, with no identifiable local or systemic cause. Since current management is often unsatisfactory, the aim of this report is to describe a new treatment modality (i.e., low-dose naltrexone [LDN]). STUDY DESIGN: A 62-year-old woman presented with the complaint of burning on the tongue of 3 years' duration. Existing comorbidities were fibromyalgia, irritable bowel syndrome, headache, and interstitial cystitis. Her reported pain intensity ranged from 2/10 (morning) to 8/10 (evening) on a numeric rating scale. With the diagnosis of BMS and hyposalivation, and in light of her current clonazepam use and fibromyalgia, a dry mouth protocol and LDN (3 mg) were prescribed. RESULTS: After 1 month, her pain intensity decreased by 50%, with no pain upon awakening. After 2 months, the widespread pain associated with her chronic morbidities also reduced by 50%, and her headache disappeared. After adjusting LDN dose to 4.5 mg, the patient was stable at 6 months, with 50% reduction of widespread pain and 2/10 BMS pain, and no reported side effects. CONCLUSIONS: These preliminary results suggest that LDN may be a feasible and effective treatment for BMS, especially in patients' refractory to traditional treatment.

[My tongue is burning!-Glossodynia/orofacial pain disorder]. / Meine Zunge brennt! ­ Glossodynie/orofaziales Schmerzsyndrom.

Glossodynia or orofacial pain disorder is known as burning mouth syndrome. It is a therapeutic challenge. Its etiology is not well defined. Recent studies show not only a correlation with neuropathic changes, but there are also indications of comorbidities such as depression, anxiety, and carcinophobia. These can also manifest as a reaction to the disease and are not necessarily considered causative. Burning mouth syndrome poses a diagnostic challenge since its differential diagnosis is broad. With regard to dermatological aspects, lichen planus mucosae, oral leucoplakia, pemphigus vulgaris, and aphthous mouth ulcers should be considered. Diabetes, anemia, vitamin deficiency, and endocrinological influences should be considered regarding the predominance of elderly and female patients. Meta-analyses of treatment studies usually show a low level of evidence of the randomized, controlled trials. According to the literature mainly psychotherapy and antidepressants are proposed for therapy. Alpha lipoic acid as a dietary supplement shows short-term improvement and low-level laser therapy might have some benefit.

Salivary characteristics in burning mouth syndrome: a systematic review.

INTRODUCTION: Compare through case-control studies, the salivary characteristics of patients with and without BMS. EVIDENCE ACQUISITION: Searches in Embase, PubMed, Web of Science, Scopus, Cochrane, and BIREME were conducted for the identification of case-controls studies reported. EVIDENCE SYNTHESIS: Thirty-three studies were included, of which 26 articles evaluated OSB, 17 SRF, and 7 SE. Nineteen organic biomarkers showed higher levels in BMS patients, the two most indicated being α-amylase and cortisol. Ten organic biomarkers, including Tumor Necrosis Factor-alpha (TNF-α) and IL-6, showed lower levels in BMS patients. Regarding salivary flow rate (SFR), five articles indicated that BMS patients have less unstimulated SFR (uSRF)Two articles indicate that stimulated SFR (sSRF) is lower in BMS patients nevertheless, but eight did not show differences. Sialochemical analysis revealed that sodium (Na), chloride (Cl), potassium (K), sodium (Na), and calcium (Ca), showed higher levels in BMS patients according to three studies, but two studies did not establish any differences. Two study established that BMS patients have lower Mg salivary levels. CONCLUSIONS: Qualitative salivary characteristics suggest that BMS has neuropathic, inflammatory, emotional, immune, and hormonal involvements. BMS can be associated with changes in salivary biomarkers of inflammation and oxidative stress, is related to anxiety and degree of pain.

Síndrome da ardência bucal: relato de caso clínico / Oral burning syndrome: a clinical case report

O presente estudo teve como objetivo principal descrever por meio de um relato de caso clínico o diagnóstico e a conduta clínica de uma paciente portadora da Síndrome da Ardência Bucal (SAB). A SAB é definida como uma dor crônica e de difícil diagnóstico e difícil tratamento. O local mais acometido pela SAB é a língua, lábios e mucosa jugal, mas pode estar presente em qualquer parte da mucosa oral, causando desconforto e interferindo na qualidade de vida do paciente. Paciente do sexo feminino, leucoderma, 39 anos, sem histórico de doenças sistêmicas, saúde geral em bom estado, procurou atendimento no Centro Universitário da Serra Gaúcha ­ FSG por apresentar sensação de ardência recorrente na língua e na mucosa, que aumentava em momentos de estresse ou durante a ingestão de alimentos cítricos, picantes ou quentes. A paciente realizou exames complementares (hemograma completo, glicemia de jejum, exame de vitamina B12) e primeiramente, iniciou-se o tratamento com antifúngico tópico para remoção de uma camada esbranquiçada presente no dorso da língua. Após a remissão desta, foi utilizado AD-Muc tópico 2 vezes ao dia, durante 2 semanas e relatou ter reduzido seus sintomas em torno de 70%. A paciente ainda apresentava xerostomia e, então foi prescrita saliva artificial. A paciente teve a regressão total de seus sintomas. Pode-se concluir que diversos fatores etiológicos estão relacionados com a SAB, porém sua causa específica permanece desconhecida. O tratamento é paliativo, entretanto, o Ad-muc tópico se mostrou eficaz na redução da sintomatologia da SAB juntamente com o uso da saliva artificial(AU)

The present study aimed to describe, through a clinical case report, the diagnosis and clinical conduct of a patient with Burning Mouth Syndrome (BMS). BMSis defined as chronic pain that is difficult to diagnose and difficult to treat. The site most affected by BMS is the tongue, lips, and cheek mucosa, but it can be present in any part of the oral mucosa, causing discomfort and interfering with the patient's quality of life. Female patient, leucoderma, 39 years old, with no history of systemic diseases, general health in good condition, sought care at the Centro Universitário da Serra Gaúcha - FSG for presenting a recurrent burning sensation in the tongue and mucosa, which increased in times of stress or while eating citrus, spicy or hot foods. The patient underwent complementary tests (complete blood count, fasting blood glucose, vitamin B12 test) and first, treatment with topical antifungal was started to remove a whitish layer present on the back of the tongue. After remission, topical AD-Muc was used twice a day for 2 weeks and reported to have reduced his symptoms by around 70%. The patient still had xerostomia and then artificial saliva was prescribed. The patient had a total regression of her symptoms. It can be concluded that several etiological factors are related to SAB, but its specific cause remains unknown. Treatment is palliative, however, topical Ad-muc is effective in reducing the symptomsof BMS also with the use of artificial saliva(AU)

Síndrome de la boca ardiente: revisión de la literatura / Burning mouth syndrome: literature review

Resumen El síndrome de la boca ardiente (SBA) es una condición de dolor crónico en la cavidad oral, que se presenta mayoritariamente en mujeres de edad media. Diversas causas locales y sistémicas pueden producirlo en forma secundaria, o bien, puede representar un cuadro primario, sin etiología específica identificable. Su etiopatogenia y evolución clínica es poco comprendida. Las opciones terapéuticas son variadas y en general es necesario un tratamiento multidisciplinario. A continuación, se presenta una revisión de la literatura respecto a esta patología para difusión en nuestro medio.

Abstract Burning mouth syndrome (BMS) is a chronic pain condition of the oral cavity, which occurs more frequently in middle-aged women. It can be secondary to different local and systemic causes, or represent a primary condition, with no specific identifiable etiology. Its etiopathogenesis and clinical evolution are poorly understood. Therapeutic options are multiple and a multidisciplinary treatment is necessary. We present a review of the literature regarding BMS, to provide information relevant to our area of expertise.

Central sensitization in burning mouth syndrome: a practical approach using questionnaires.

OBJECTIVES: Some experts have suggested that burning mouth syndrome (BMS) should be included in the family of central sensitivity syndromes, a group of similar medical disorders linked by the central sensitization (CS) mechanism. Our objective is to assess the presence of CS in patients with BMS by performing a clinical examination and administering questionnaires to measure the generalized extent of pain, the presence of associated symptoms, and the number of other concurrent chronic pain conditions. STUDY DESIGN: We conducted a case-control study in 82 subjects (40 patients with BMS and 42 controls). Patients with BMS were diagnosed using The International Classification of Headache Disorders 3rd edition, beta version (ICHD-IIIß) criteria. The Widespread Pain Index (WPI) and Symptom Severity (SS) Score questionnaires were used to determine the degree of central sensitivity. The number of other concurrent chronic pain conditions was determined with the Neblett inventory. RESULTS: Data indicative of CS show a statistically significant association with BMS. Both SS Score and Widespread Pain Index scores higher in patients with BMS. Additionally, patients with BMS reported a significantly higher number of other central sensitivity syndromes. CONCLUSIONS: Patients with BMS could present a CS component as well as other chronic pain conditions. The use of questionnaires may be useful to determine the degree of central sensitivity in patients with BMS.

Impact of the COVID-19 pandemic upon patients with burning mouth syndrome.

INTRODUCTION: The global COVID-19 pandemic has caused changes in the daily life of people, with a particularly relevant impact upon certain groups of individuals that have difficulties in facing stress. A study is made of the impact of the pandemic upon patients with burning mouth syndrome (BMS). MATERIAL AND METHODS: A total of 40 patients with BMS diagnosed in the Unit of Oral Medicine (University of Murcia, Spain) were included. In all cases the study comprised a standardized clinical interview by the same professional and an exploration of the oral cavity. The first visit took place before the pandemic and consisted of the evaluation of anxiety (Hospital and Anxiety Depression Scale [HADS]), the Pain Catastrophizing Scale (PCS), pain intensity (visual analog scale [VAS]) and sleep quality (Pittsburg Sleep Quality Index [PSQI]), while the second visit took place one and a half months after the start of lockdown due to the pandemic in Spain. RESULTS: The study sample consisted of 36 women (90%) and four men (10%) aged between 39 and s86 years. Statistically significant differences were recorded between the two visits in terms of anxiety (p < 0.001), sleep quality (p < 0.001) and pain intensity (p < 0.001). CONCLUSIONS: The appearance of the COVID-19 pandemic has triggered worsening of anxiety, sleep quality and pain intensity in patients with BMS.

Neuropathic orofacial pain: Characterization of different patient groups using the ICOP first edition, in a tertiary level Orofacial Pain Clinic.

OBJECTIVE: To characterize patients with chronic neuropathic orofacial pain in accordance with the International Classification of Orofacial Pain (ICOP first edition) criteria. STUDY DESIGN: A retrospective chart review of 108 patients was conducted. The most common categories observed were trigeminal neuralgia (TN) (25.9%), burning mouth syndrome (BMS) (11.1%), persistent idiopathic facial pain (PIFP) (26.9%), and posttraumatic trigeminal neuropathic pain (PTTNP) (26.9%); 9.3% of patients could not be categorized. RESULTS: TN and BMS was more prevalent in the sixth decade, and PIFP and PTTN were more prevalent in the fifth decade. All categories showed female predilection. The pain in TN was predominantly episodic, described as "sharp shooting" and like an "electric shock," unilateral and affecting the V2 division, and with trigger zones in 50% of patients. Pain in BMS was predominantly constant and described as "burning," with the tongue being the most common site. Pain in PIFP and PTTNP was as follows: varied from constant to episodic; described as "burning," "sharp shooting," "throbbing," or "dull aching"; intraoral or extraoral; and mostly involving the V2 or V3 division. CONCLUSION: This study is the first to characterize patients with neuropathic orofacial pain using the new ICOP criteria. PIFP and PTTNP were most commonly misdiagnosed categories. Using diagnostic criteria will increase the understanding of this patient group.

Prediction of treatment outcome in burning mouth syndrome patients using machine learning based on clinical data.

The purpose of this study is to apply a machine learning approach to predict whether patients with burning mouth syndrome (BMS) respond to the initial approach and clonazepam therapy based on clinical data. Among the patients with the primary type of BMS who visited the clinic from 2006 to 2015, those treated with the initial approach of detailed explanation regarding home care instruction and use of oral topical lubricants, or who were prescribed clonazepam for a minimum of 1 month were included in this study. The clinical data and treatment outcomes were collected from medical records. Extreme Gradient-Boosted Decision Trees was used for machine learning algorithms to construct prediction models. Accuracy of the prediction models was evaluated and feature importance calculated. The accuracy of the prediction models for the initial approach and clonazepam therapy was 67.6% and 67.4%, respectively. Aggravating factors and psychological distress were important features in the prediction model for the initial approach, and intensity of symptoms before administration was the important feature in the prediction model for clonazepam therapy. In conclusion, the analysis of treatment outcomes in patients with BMS using a machine learning approach showed meaningful results of clinical applicability.

Evaluation of a Protocol For Topical Application of Capsaicine Gel 0.025 % in the Management of Burning Mouth Syndrome Correlating its Impact on Quality of Life / Evaluación de un Protocolo de Aplicación Tópica de Capsaicina Gel 0, 025 % en el Tratamiento del Síndrome de Boca Ardiente Correlacionando su Impacto con la Calidad de Vida

The aim of this study is to report the results obtained with a protocol of topical application of capsaicin gel 0.025 % in the management of burning mouth syndrome (BMS) to evaluate the influence of the disease and treatment on their quality of life (QOL) using the OHIP-14 questionnaire (Oral Health Impact Profile). After clinical examination and diagnosis of BMS, 10 patients reported the intensity of the burning by means of a subjective score ranging from 0 to 10 and also answered the OHIP-14. Then, a topical application protocol of capsaicin gel 0.025 % was initiated, with weaning from medication and complete withdrawal within 180 days. At each reassessment consultation (30, 60, 90 and 180 days), the patients answered the OHIP-14 and subjective burning scores were collected again. Overall, the capsaicin gel showed gradual reduction or elimination of symptoms of BMS, as well as an improvement in the QOL of patients throughout treatment. At 180 days, after medication withdrawal, 6 patients (60 %) reported total absence of burning and in four patients (40 %) the score remained or decreased. In one patient (10 %) the score increased, although it remained below the initial score. The results showed an improvement in the QOL of all patients who completed the protocol and the impact of BMS on the QOL decreased in relation to the initial score in all patients. The topical use of 0.025 % capsaicin gel was effective in reducing or remitting symptoms of BMS. The OHIP-14 questionnaire showed the negative impact of BMS on patients' QOL and the role of treatment in its improvement.

El objetivo de este estudio fue reportar los resultados obtenidos con un protocolo de aplicación tópica de gel de capsaicina al 0,025 % en el manejo del síndrome de boca ardiente (SBA), para evaluar la influencia de la enfermedad y el tratamiento en su calidad de vida (CV) mediante el cuestionario OHIP-14. Tras el examen clínico y diagnóstico de SBA, 10 pacientes refirieron la intensidad del ardor mediante una puntuación subjetiva de 0 a 10 y también respondieron la OHIP-14. Luego, se inició un protocolo de aplicación tópica de gel de capsaicina al 0,025%, con destete de la medicación y retiro completo en 180 días. En cada consulta de reevaluación (30, 60, 90 y 180 días), los pacientes respondieron el OHIP-14 y se recogieron nuevamente las puntuaciones subjetivas de quemado. En general, el gel de capsaicina mostró una reducción o eliminación gradual de los síntomas del SBA, así como una mejora en la calidad de vida de los pacientes durante todo el tratamiento. A los 180 días, después de la retirada de la medicación, 6 pacientes (60 %) informaron ausencia total de ardor y en cuatro pacientes (40%) la puntuación se mantuvo o disminuyó. En un paciente (10 %) la puntuación aumentó, aunque se mantuvo por debajo de la puntuación inicial. Los resultados mostraron una mejora en la CV de todos los pacientes que completaron el protocolo y el impacto de SBA en la CV disminuyó en relación con la puntuación inicial en todos los pacientes. El uso tópico de gel de capsaicina al 0,025 % fue efectivo para reducir o remitir los síntomas del SBA. El cuestionario OHIP-14 mostró el impacto negativo de SBA en la CV de los pacientes y el papel del tratamiento en su mejora.

Anatomically Coiled Internal Carotid Artery Resulting in Severe Dysphagia and Burning Mouth Syndrome.

This is a report of a 65-year-old female presenting with symptoms of dysphagia due to a coiled left internal carotid artery, treated with resection and primary repair. Dysphagia lusoria is more commonly caused by aortic arch anomalies, aberrant subclavian or common carotid arteries. Internal carotid tortuosity as a cause of severe dysphagia and burning mouth syndrome is highly unusual. A literature review examines the etiology, natural history, and treatment options.

Is Burning Mouth Syndrome Based on a Physiological Mechanism which Resembles that of Neuropathic Pain? / Comparación entre el mecanismo fisiológico del síndrome de la boca ardiente y el dolor neuropático

Abstract: Burning mouth syndrome (BMS) is a chronic intraoral pain state that has been described as burning pain, tingling or numbness in the oral mucosa, in the absence of any organic disease. Most often affecting the tongue, anterior palate, and/or lips. The diagnosis of primary BMS is purely clinical and based on patients' description of typical subjective symptoms as well on the exclusion of any systemic or local factors that may give rise to secondary burning pain sensations within the oral mucosa. Relevant studies links BMS to a peripheral neuropathy and BMS patients have revealed distinct abnormalities within the trigeminofacial large and small fiber systems and the trigeminal brainstem complex. Therefore, treatment approach should involve a multidisciplinary character similar to the treatment for neuropathic pain including factors that might also play a role on the BMS etiology and pathophysiology.

Resumen: El síndrome de la boca ardiente (SBA) es un estado crónico de dolor intraoral descrito por pacientes como dolor o sensación quemante, de cosquilleo o adormecimiento de la mucosa oral, con ausencia de lesiones visibles en la boca. Puede afectar la lengua, el paladar anterior y o los labios. Su diagnóstico es basado en la típica descripción subjetiva del paciente, excluyendo cualquier otro factor sistémico o local que podría provocar cualquier otra sensación quemante dentro de la mucosa oral. Estudios relevantes han mostrado que SBA primario parece tener una patofisiología de origen de tipo neuropático donde pacientes con SBA pueden presentar distintas anormalidades en el complejo trigeminal a nivel de las fibras sensoriales delgadas y gruesas. Por tanto, el tratamiento y manejo de estos pacientes debe ser de la misma manera multidisciplinaria como en el caso con el dolor neuropático, sin olvidar incluir el manejo de todos los factores que podrían intervenir en la etiología del SBA.

Nondental orofacial pain in dental practices - diagnosis, therapy and self-assessment of German dentists and dental students.

BACKGROUND: Patients with non-dental orofacial pain syndromes will often primarily consult general dentists and other dental specialists. Early and correct diagnosis and therapy is crucial to prevent chronification. METHODS: We assessed the experience of dentists (general dentists and dental specialists; n = 533) and knowledge level of dental students (n = 130) on the diagnosis and treatment of non-dental orofacial pain. We used an anonymized survey containing 14 items with the four main themes (1) prescription patterns, (2) treatment strategies in non-dental orofacial pain, (3) interdisciplinary cooperation, and (4) self-assessment of knowledge as well as post-graduate education. RESULTS: Ninety-two percent of dental students stated that they feel either 'not at all' (56%) or only 'somewhat' (36%) prepared for the diagnosis or treatment of non-dental orofacial pain. Only 23% of the dentists reported 'good' or 'very good' confidence for the diagnosis of non-dental orofacial pain. NSAID were the analgesics of choice when the pain is unspecific (25%) or even neuralgic (10%). Dentists referred patients with non-dental orofacial pain mostly to ENT-physicians (59%), oral and maxillofacial surgeons (54%) or TMD specialists (51%). CONCLUSION: Interdisciplinary pain treatment seems to be well acknowledged, however, with a focus on referral within the community of dental specialists. Dental curricula and post-graduate trainings need to implement the diagnosis and treatment options of non-dental orofacial pain.