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Burning mouth syndrome (BMS) is a chronic oro-facial pain disorder of unknown cause. It is more common in peri-and post-menopausal women, and sex hormone dysregulation is believed to be an important causative factor. Psychosocial events often trigger or exacerbate symptoms, and persons with BMS appear to be predisposed towards anxiety and depression. Atrophy of small nerve fibres in the tongue epithelium has been reported, and potential neuropathic mechanisms for BMS are now widely investigated. Historically, BMS was thought to comprise endocrinological, psychosocial and neuropathic components. Neuroprotective steroids and glial cell line-derived neurotrophic factor family ligands may have pivotal roles in the peripheral mechanisms associated with atrophy of small nerve fibres. Denervation of chorda tympani nerve fibres that innervate fungiform buds leads to alternative trigeminal innervation, which results in dysgeusia and burning pain when eating hot foods. With regard to the central mechanism of BMS, depletion of neuroprotective steroids alters the brain network-related mood and pain modulation. Peripheral mechanistic studies support the use of topical clonazepam and capsaicin for the management of BMS, and some evidence supports the use of cognitive behavioural therapy. Hormone replacement therapy may address the causes of BMS, although adverse effects prevent its use as a first-line treatment. Selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) may have important benefits, and well-designed controlled studies are expected. Other treatment options to be investigated include brain stimulation and TSPO (translocator protein 18 kDa) ligands. K E Y W O R D Sburning mouth syndrome, central pain modulation, menopause, neuroprotective steroids | 575 IMAMURA et Al. | INTRODUC TI ONBurning mouth symptoms that occurred as secondary phenomena attributable to local conditions 1-9 were previously referred to as "secondary" burning mouth syndrome (BMS), 10 but BMS now refers only to burning symptoms not attributable to local or systemic causes. 11 After excluding such conditions, some common characteristics of BMS are important. Burning sensations are usually bilateral, and intensity fluctuates. 2 The most common site is the tip of the tongue, but pain is often noted at the lateral border of the tongue, lips and hard palate. 12 Affected persons often complain of dysgeusia, 13 which may be accompanied by subjective xerostomia. 14 Peri-and post-menopausal women are predisposed to the condition.Some patients exhibit depressive symptoms and anxiety 15-18 and may express concern regarding the presence of a malignant condition. 10,16 Psychosocial stressors can trigger or worsen pain, 15,19 while eating and drinking usually alleviate pain. 10,20 These manifestations are characteristic features of BMS and should not be excluded as secondary signs or symptoms of primary disease. Agreement on these clinical features yields important clues in understanding the underlying pathoph...

The significance of heart-rate turbulence (HRT) in patients with chronic heart failure (CHF) was evaluated to examine whether it is sensitive to the risk of ventricular tachycardia (VT). HRT is reported to predict the prognosis after myocardial infarction (MI), but its prognostic value in patients with CHF remains unknown. HRT was measured in 50 CHF patients (left ventricular ejection fraction <50% and/or left ventricular end-diastolic diameter >55 mm, 34 cardiomyopathy, 16 post-MI) and 21 patients without obvious heart diseases (control). HRT slope and HRT onset were measured by the original definitions using digitized Holter ECG recordings. Cardiac pump function was assessed by echocardiography. The value of the HRT slope was significantly lower in CHF than in control (3.7 +/- 1.7 vs 16.4 +/- 5.3, mean +/- SD, p < 0.01). The value of the HRT onset in patients with CHF was significantly higher than that in control patients (-1.1 +/- 1.9 vs -3.6 +/- 1.7, mean +/- SD, p < 0.05). The HRT slope and onset in CHF patients with VT were nearly identical to those without VT. The HRT slope appears to be a powerful prognostic marker that shows significant differences between CHF subgroups when divided by clinical events; that is, CHF death and CHF hospitalization. However, it has limited value for predicting fatal ventricular arrhythmias.

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Burning mouth syndrome (BMS) is an idiopathic orofacial pain condition. Although the pathophysiology of BMS is not clearly understood, central and peripheral neuropathic mechanisms are thought to be involved. The authors compared brain response to noxious heat stimuli in 16 right-handed women with primary BMS and 15 sex- and age-matched right-handed healthy female controls. A thermal stimulus sequence of 32 °C to 40 °C to 32 °C to 49 °C was repeated 4 times in a cycle. Warm and noxious heat stimuli were delivered with a Peltier thermode placed on the right palm or right lower lip for 32 s each in a session. Functional magnetic resonance imaging data were obtained by recording echoplanar images with a block design. Statistical Parametric Mapping 8 software was used to analyze the data. Patients and controls both reported feeling more pain during palm stimulation than during lip stimulation. Repetition of noxious heat stimulus on the lower lip but not on the palm induced habituation in brain activity in the cingulate cortex without reduction in pain perception. Multiple regression analysis revealed a correlation between perceived pain intensity and suppression of brain activity in the anterior cingulate cortex when the repeated thermal sequence was applied at the lower lip. Furthermore, the response of the parahippocampal area differed in BMS patients and controls when the same repeated thermal sequence was applied at the palm. The authors' findings indicate that BMS patients show specific brain responses due to impaired function of the central and peripheral nervous systems (clinical trial registration: UMIN000015002).

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