PAR2-dependent phosphorylation of TRPV4 at the trigeminal nerve terminals contributes to tongue cancer pain.

OBJECTIVE: This study aimed to clarify the interactions between the tongue and primary afferent fibers in tongue cancer pain. METHODS: A pharmacological analysis was conducted to evaluate mechanical hypersensitivity of the tongues of rats with squamous cell carcinoma (SCC). Changes in trigeminal ganglion (TG) neurons projecting to the tongue were analyzed using immunohistochemistry and western blotting. RESULTS: SCC inoculation of the tongue caused persistent mechanical sensitization and tumor formation. Trypsin expression was significantly upregulated in cancer lesions. Continuous trypsin inhibition or protease-activated receptor 2 (PAR2) antagonism in the tongue significantly inhibited SCC-induced mechanical sensitization. No changes were observed in PAR2 and transient receptor potential vanilloid 4 (TRPV4) levels in the TG or the number of PAR2-and TRPV4-expressing TG neurons after SCC inoculation. In contrast, the relative amount of phosphorylated TRPV4 in the TG was significantly increased after SCC inoculation and abrogated by PAR2 antagonism in the tongue. TRPV4 antagonism in the tongue significantly ameliorated the mechanical sensitization caused by SCC inoculation. CONCLUSIONS: Our findings indicate that tumor-derived trypsin sensitizes primary afferent fibers by PAR2 stimulation and subsequent TRPV4 phosphorylation, resulting in severe tongue pain.

Síndrome de boca ardiente, abordaje otorrinolaringológico. Revisión bibliográfica sistemática / Burning mouth syndrome, otorhinolaryngological approach. Systematic literature review

Introducción y objetivo: El síndrome de boca ardiente (SBA) es una afección crónica, que cursa con quemazón o dolor de la mucosa bucal, afectando predominantemente a mujeres de edad media. Puede aparecer como cuadro primario o bien de forma secundaria. La fisiopatología de esta entidad es bastante desconocida. Existe un amplio abanico terapéutico, pero por lo general precisa de un abordaje multidisciplinar. Nuestra intención es realizar una puesta al día de la enfermedad para poder hacerla frente en la consulta de otorrinolaringología. Método: Revisión bibliográfica de la literatura. Fecha de publicación limitada de 2012 a 2022. Resultados: El SBA presenta una etiopatogenia de carácter multifactorial. Para su diagnóstico es necesario realizar una exhaustiva anamnesis y exploración. Se diferencian 3 tipos distintos de SBA, siendo el tipo II el más frecuente y el más refractario a la terapia. El adecuado tratamiento se fundamenta en un correcto diagnóstico y debe ser multidisciplinar. Discusión: Es importante resaltar que es una entidad benigna. Los tratamientos son variados y no hay ninguno que destaque sobre el resto, lo que dificulta el manejo de estos pacientes. Aunque la bibliografía sobre este síndrome es abundante, no se han producido en los últimos años, importantes innovaciones en cuanto a la etiología y tratamiento. Conclusiones: La anamnesis y los estudios de laboratorio son fundamentales para descartar casusas secundarias de la enfermedad. La terapia es diversa y debe incluir derivación a salud mental como parte del manejo multidisciplinar. (AU)

Introduction and objective: Burning mouth syndrome (BMS) is a chronic condition that causes burning or pain of the oral mucosa, predominantly affecting middle-aged women. It can appear as a primary box or secondary. The pathophysiology of this entity is quite unknown. There is a varied therapeutic range, but it generally requires a multidisciplinary approach. Our intention is to update the disease in order to deal with it in the otorhinolaryngology consultation. Method: Bibliographic review of the literature. Limited release date from 2012 to 2022. Results: BMS has a multifactorial etiopathogenesis. For its diagnosis it is necessary to carry out an exhaustive anamnesis and examination. There are 3 different types of BMS, type II being the most frequent and the most refractory to therapy. Adequate treatment is based on a correct diagnosis and must be multidisciplinary. Discussion: It is important to emphasize that it is a benign entity. The treatments are varied and there is none that stands out above the rest, which makes it difficult to manage these patients. Although the bibliography on this syndrome is abundant, important innovations in terms of etiology and treatment have not been produced in recent years. Conclusions: Anamnesis and laboratory studies are essential to rule out secondary causes of the disease. Therapy is varied and should include referral to mental health as part of multidisciplinary management. (AU)

Prevalencia de glosodinia. Síndrome de boca ardiente y factores de riesgo asociados en la población de Ciudad Real / Prevalence of glossodynia. Burning mouth syndrome and associated risk factors in the population of Ciudad Real

Objetivo: Conocer la prevalencia real del síndrome de boca ardiente (SBA) y los posibles factores de riesgo asociados.Material y métodos: Estudio observacional descriptivo transversal, de base poblacional con selección aleatoria simple en mayores de 24 años. Tras muestreo aleatorio, el año 2015 se contactó telefónicamente identificando pacientes que cumplían criterios de inclusión. A estos se les realizó entrevista presencial, descartando presencia de lesiones orales, se realizó test de ansiedad, depresión y analítica. Se agregó una cohorte de pacientes ya diagnosticados de base de datos del Hospital de Ciudad Real de Dermatología, para analizar los posibles factores de riesgo asociados comparando con un grupo control. Las características de los pacientes con SBA y los controles sin SBA se analizaron estadísticamente con el SPSS v 21 y se utilizaron la prueba de Chi cuadrado y el Odds Ratio (OR) para evaluar las diferencias en las características de losgrupos. La significación estadística se fijó en p < 0,05.Resultados: La prevalencia fue de 0,84 % (IC 95 %: 0,28-1,4). Los factores que alcanzaron significación estadística en el desarrollo de SBA fueron los siguientes: el sexo femenino p < 0,05 (IC 1,43-2,20), antecedentes de ansiedad p < 0,05 (IC 6,4-72,47), depresión p < 0,05 (IC 3,59-34,40 ), de candidiasis oral p < 0,05 (IC 1,44-16,27), de déficit nutricional p < 0,05 (IC 4,1-100,05), miedo al cáncer p < 0,05 (IC 1-1,36), hipotiroidismo p < 0,005 (IC 1,06-31,48) y uso de prótesis dentales p < 0,05 (IC 1,06-32,48). La toma de antidepresivos p < 0,05 (IC 7,28-177,86) y ansiolíticos p < 0,05 (IC 7,56-99,67). La presencia de sequedad bucal subjetiva p < 0,05 (IC 1,81-17,94) y objetiva p < 0,05 (IC 1,47-14,57). Tener alterados los cuestionario de ansiedad p < 0,05 (IC 10,64-183,29) y depresión p < 0,05 (IC: 5,48-132,92).(AU)

Objective: To know the real prevalence of burning mouth syndrome (BAS) and the possible associated risk factors.Material and methods: Observational, descriptive, cross-sectional, population-based study with simple random selection in people over 24 years of age. After showing up randomly, in 2015 a telephone call was made to identify patients who met the inclusion criteria. They underwent a face-to-face interview, ruling out the presence of oral lesions, anxiety, depression and analytical tests were performed. A cohort of patients already diagnosed from the Ciudad Real Dermatology Hospital database was added to analyze the possible associated risk factors compared with a control group. Characteristics of BMS patients and non-ABS controls were statistically analyzed with SPSS v 21 and chi-square test and Odds Ratio (OR) were used to assess differences in group characteristics. Significance statistic was set at p < 0.05.Results: The prevalence was 0.84 % (95 % CI 0.28-1.4). The factors that reached statistical significance in the development of BMS were the following: female sex p < 0.05 (CI 1.43-2.20), history of anxiety p < 0.05 (CI 6.4-72.47) depression p < 0.05 (CI 3.-34.40), oral candidiasis p < 0.05 (CI 1.44-16.27); and nutritional deficit p < 0.05 (CI 4.1-100.05); fear of cancer p < 0.05 (CI 1-1.36); hypothyroidism p < 0.05 (CI 1.06-31.48) and use of dental prostheses p < 0.05 (CI 1.06-32,48). Taking antidepressants p < 0.05 CI (7.28-177.86) and anxiolytics p < 0.05 (CI 7.56-99.67). The presence of subjective dry mouth p < 0.05 (IC 1.81-17,94) and objective p < 0.05 (IC 1.47-14.57). Having altered the Anxiety Questionnaire p < 0.05 (CI 10.64-183.29); and depression p < 0.05 (CI: 5.48-132.92).(AU)

[Clinical aspects of diagnosis and treatment of glossodynia in elderly and senile people.]

Glossodynia is a disease that is difficult to diagnose and treat. Persons of older age groups are in the most risk of its occurrence. This is due to the fact that its etiological factors are: age-related changes, general somatic diseases, usage of some pharmacological drugs, changes in the psycho-emotional background. Due to the similarity of the clinical picture of glossodynia with other diseases of the oral cavity, the doctor is required to be thoughtful when diagnosing and differentiating glossodynia. Clinical methods of examination are used, paying most attention to the anamnesis of life and disease, assessment of the personal and emotional sphere of the patient. Clinico-functional, clinico-instrumental, and laboratory methods of examination are also used. In the treatment of glossodynia, attention should be paid not only to the elimination of symptoms, but also to its prevention. The main efforts should be aimed at combating the main links of pathogenesis. Treatment should be comprehensive, differentiated and personalized. As a result of many researchers work, certain principles of diagnostics and treatment of glossodynia have been developed, which will be considered in our work.

[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.

Unilateral glossodynia as a harbinger of an occult cerebellopontine angle tumour.

A woman in her late 80s with severe bronchomalacia was referred to a tertiary orofacial pain clinic for unexplained right unilateral glossodynia of progressive and continuous evolution for the past 8 months, spreading to the ipsilateral labiomental region, associated with ipsilateral hypoacusia. Local and general clinical examinations were unremarkable and routine blood work could not reveal any underlying systemic disease explaining the glossodynia and burning/pricking labiomental pain. Suspecting a painful trigeminal neuropathy secondary to a space-occupying lesion, a cerebral MRI was prescribed, revealing an ipsilateral cerebellopontine angle lesion, compatible with either a schwannoma or meningioma. This lesion invaded the root entry zones of cranial nerves V and VIII explaining the patient's oral pain and hypoacusia. Following a neurosurgical consultation where surgical treatment was rejected, her pain was successfully managed by topical pregabalin mouthwashes, to prevent any risk of respiratory depression related to her underlying severe bronchomalacia.

Glossodynia, burning mouth syndrome, and COVID-19.

PURPOSE: To evaluate whether the prevalence of glossodynia increased among patients affected by COVID-19 compared to other hospital populations. METHODS: The i2b2 patient registry platform at the University of Florida Health Center was used to generate a count of patients using the international classification of diseases (ICD)-10 diagnosis codes from October 2015 to June 2021. Logistic regression of the aggregates was used for analysis. RESULTS: Of the patients with both glossodynia and COVID-19, 60% were females, 32% were African American, 64% were white, and 100% were adults. There were 72% females, 19% African Americans, 72% whites, and 93% adults with glossodynia only. For COVID-19 patients, 57% were females, 23% were African American, 56% whites, and 90% were adults. The odds ratio (OR) for glossodynia in the COVID-19 patients was significant (OR = 2.9; 95% CI, 1.94-4.32; P < 0.0001). CLINICAL SIGNIFICANCE: Glossodynia is significantly more common in COVID-19 patients and should be considered in the differential diagnoses among the oral complications of this infection.

[Pain syndromes and insomnia: the role of association with comorbid mental disorders (on the model of glossalgia)]. / Bolevye sindromy i insomniya: rol' assotsiatsii s komorbidnymi psikhicheskimi rasstroistvami (na modeli glossalgii).

OBJECTIVE: To test the association between pain severity and anxiety, depression, and somatoform symptoms in burning sleep syndrome (BMS). MATERIAL AND METHODS: The study included 36 patients (33 women, 3 men), mean age 58.0±14.8 years. Psychopathological, clinical-dermatological, parametric, statistical methods were used. Psychometric examination included the Visual Analogue Scale (VAS) for assessment of pain (severity of glossalgia), PHQ-4 for self-assessment of severity of anxiety (GAD-2) and depression (PHQ-2), the Hospital Anxiety and Depression Scale (HADS), the Screening for Somatoform Symptoms-2 (SOMS-2), the Pittsburgh Sleep Quality Index (PSQI), the EQ-5D-5L quality of life assessment scale. RESULTS AND CONCLUSION: Insomnia in chronic pain is very common. On the one hand, studies show that sleep deprivation can enhance pain perception. On the other hand, chronic pain can trigger a variety of sleep disorders. One of the localizations of chronic pain syndrome is the oral mucosa. Somatoform pain disorder related to oral mucosa called «glossalgia¼ or «burning mouth syndrome¼ (BMS). The prevalence of insomnia in the study sample was 61.1%. The statistically significant positive correlation was found between the severity of insomnia (PSQI) and the severity of anxiety on both GAD-2 and HADS, while insomnia showed no correlation with depression and pain severity. At the same time, the severity of anxiety showed statistically significant positive correlation with the severity of pain assessed by VAS.

[Glossalgia as a psychodermatological syndrome]. / Glossalgiya kak sindrom psikhodermatologicheskoi patologii.

OBJECTIVE: To study clinical characteristics of burning mouth syndrome or glossalgia is a functional disorder with painful sensations in the oral cavity with verification of the psychopathological structure, typology and nosology of the syndrome within the continuum of neurotic/psychotic disorders and dermatological pathology, i.e. lichen planus (LP). MATERIAL AND METHODS: The study sample (n=30, 27 female, mean age 59.3±15.6 years) was examined by dermatologist, neurologist and psychiatrist both clinically and psychometrically. The patients met the diagnostic criteria for glossalgia according to the IASP classification and ICD-10 for glossodynia (code K14.6). In 7 subjects, there was comorbidity with LP of the oral mucosa. RESULTS: The psychopathological picture of glossalgia syndrome has a binary structure. Basic coenesthesiopathies, ranging in severity from homonomous sensations (isteralgias) to heteronomic sensopathies (senestopathies, senesthesia), are associated with secondary hypochondriacal phenomena: from health anxiety and monopatophobia to mastery of ideas and somatopsychic confusion, respectively. According to the psychopathological register (neurotic/psychotic) and the fact of objective verification of a dermatological disease (hypochondria sine materia/cum materia), there are three types of glossalgic syndrome: 1) organo-neurotic; 2) somatopsychotic; 3) dermatological (stress-induced somatic reactions). CONCLUSION: BMS is a local syndrome limited to the oral cavity, however, in fact, it covers the entire clinical spectrum of psychosomatic pathology from mental diseases to psychodermatological ones.

A 78-year-old female with severe tongue pain: benefit of modern ultrasound.

BACKGROUND: Giant cell arteritis (GCA) is the most common form of systemic vasculitis in persons aged 50 years and older. Medium and large vessels, like the temporal and axillary arteries, are commonly affected. Typical symptoms are headache, scalp tenderness, jaw claudication and ophthalmological symptoms as loss of visual field, diplopia or amaurosis due to optic nerve ischemia. Tongue pain due to vasculitic affection of the deep lingual artery can occur and has so far not been visualized and followed up by modern ultrasound. CASE PRESENTATION: We report the case of a 78-year-old woman with typical symptoms of GCA, such as scalp tenderness, jaw claudication and loss of visual field, as well as severe tongue pain. Broad vasculitic affection of the extracranial arteries, vasculitis of the central retinal artery and the deep lingual artery could be visualized by ultrasound. Further did we observe a relevant decrease of intima-media thickness (IMT) values of all arteries assessed by ultrasound during follow-up. Especially the left common superficial temporal artery showed a relevant decrease of IMT from 0.49 mm at time of diagnosis to 0.23 mm on 6-months follow-up. This is the first GCA case described in literature, in which vasculitis of the central retinal artery and the lingual artery could be visualized at diagnosis and during follow-up using high-resolution ultrasound. CONCLUSION: High-resolution ultrasound can be a useful diagnostic imaging modality in diagnosis and follow-up of GCA, even in small arteries like the lingual artery or central retinal artery. Ultrasound of the central retinal artery could be an important imaging tool in identifying suspected vasculitic affection of the central retinal artery.