Background: Due to its common association with chronic pain experience, cognitive impairment (CI) has never been evaluated in patients with burning mouth syndrome (BMS). The purpose of this study is to assess the prevalence of CI in patients with BMS and to evaluate its relationship with potential predictors such as pain, mood disorders, blood biomarkers, and white matter changes (WMCs).Methods: A case-control study was conducted by enrolling 40 patients with BMS and an equal number of healthy controls matched for age, gender, and education. Neurocognitive assessment [Mini Mental State Examination (MMSE), Digit Cancellation Test (DCT), the Forward and Backward Digit Span task (FDS and BDS), Corsi Block-Tapping Test (CB-TT), Rey Auditory Verbal Learning Test (RAVLT), Copying Geometric Drawings (CGD), Frontal Assessment Battery (FAB), and Trail Making A and B (TMT-A and TMT-B)], psychological assessment [Hamilton Rating Scale for Depression and Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and 36-Item Short Form Health Survey (SF-36)], and pain assessment [Visual Analogic Scale (VAS), Total Pain Rating index (T-PRI), Brief Pain Inventory (BPI), and Pain DETECT Questionnaire (PD-Q)] were performed. In addition, blood biomarkers and MRI of the brain were recorded for the detection of Age-Related WMCs (ARWMCs). Descriptive statistics, the Mann-Whitney U-test, the Pearson Chi-Squared test and Spearman's correlation analysis were used.Results: Patients with BMS had impairments in most cognitive domains compared with controls (p < 0.001^**) except in RAVLT and CGD. The HAM-D, HAM-A, PSQI, ESS, SF-36, VAS, T-PRI, BPI and PD-Q scores were statistically different between BMS patients and controls (p < 0.001^**) the WMCs frequency and ARWMC scores in the right temporal (RT) and left temporal (LT) lobe were higher in patients with BMS (p = 0.023^*).Conclusions: Meanwhile, BMS is associated with a higher decline in cognitive functions, particularly attention, working memory, and executive functions, but other functions such as praxis-constructive skills and verbal memory are preserved. The early identification of CI and associated factors may help clinicians to identify patients at risk of developing time-based neurodegenerative disorders, such as Alzheimer's disease (AD) and vascular dementia (VD), for planning the early, comprehensive, and multidisciplinary assessment and treatment.

Background: The symptomatology in Burning Mouth Syndrome (BMS) is complex and it should be considered in accordance with a biopsychosocial model.Objectives: To evaluate the multidimensional aspects of pain with a complete battery of tests and to analyse its relationship with potential predictors such as mood disorders, sleep and quality of life.Methods: Forty patients with BMS versus an equal number of age and sex‐matched healthy controls were enrolled. The VAS, SF‐MPQ, BPI, PD‐Q, BDI‐II, STAI, PSQI, ESS, SF‐36 and OHIP‐14 were administered.Results: The scores of the VAS, SF‐MPQ, BPI, PD‐Q, BDI‐II, STAI, PSQI, SF‐36 and OHIP‐14 were statistically significantly higher in the BMS patients than the controls (p < .001**). A strongly linear correlation between pain (VAS, SF‐MPQ, BPI and PD‐Q) and disease onset (STAI, BDI‐II, PSQI and sub‐items of SF‐36 and OHIP‐14) was found. In the multiple regression analysis, the contributions of the BDI‐II and OHIP‐14 were found to be statistically significant with the SF‐MPQ, PD‐Q and BPI in terms of severity and interference, while the contributions of the STAI and sleep were found to be statistically significant with the SF‐MPQ and BPI in terms of severity and interference, respectively.Conclusions: Pain tests are differently correlated with mood and quality of life. Therefore, a complete analysis of the patient requires several tools to better understand the multidimensional aspects of pain in BMS.

Objectives: To assess the diagnostic delay, the number and type of referrals and the clinical and psychological profile in a wide sample of patients with Burning Mouth Syndrome (BMS).Materials and Methods: Data on the disease onset, oral symptoms, type and number of practitioners consulted, misdiagnoses, and the presence of medically unexplained extraoral physical symptoms were recorded in 500 BMS patients. Potential predictors of diagnostic delay were also evaluated.Results: The mean diagnostic delay was 29.71 ± 47.19 months. An average of 2.61 ± 1.65 practitioners were consulted by each patient, the most frequent being the general physicians (287; 57.4%), maxillofacial surgeons (111; 22.2%), and otolaryngologists (104; 20.8%). The mean number of misdiagnoses was 3.54 ± 1.85. Nonspecific stomatitis, candidiasis, and gastroesophageal reflux were the most common misdiagnoses. Higher age, low education, the presence of dysgeusia, and a previous history of psychiatric illness were predictors of a longer diagnostic delay (p‐value: 0.028, 0.050, 0.007, 0.034, respectively).Conclusions: The lack of knowledge among specialists, the high rate of misdiagnosis, and the diagnostic delay of BMS highlight the need to introduce educational interventions in all medical specialties in order to promote an early and appropriate diagnosis, thereby improving the prognosis and quality of life of the patients.

Background: White matter hyperintensities (WMHs) of the brain are observed in normal aging, in various subtypes of dementia and in chronic pain, playing a crucial role in pain processing. The aim of the study has been to assess the WMHs in Burning Mouth Syndrome (BMS) patients by means of the Age-Related White Matter Changes scale (ARWMCs) and to analyze their predictors.Methods: One hundred BMS patients were prospectively recruited and underwent magnetic resonance imaging (MRI) of the brain. Their ARWMCs scores were compared with those of an equal number of healthy subjects matched for age and sex. Intensity and quality of pain, psychological profile, and blood biomarkers of BMS patients were further investigated to find potential predictors of WMHs. Specifically, the Numeric Rating Scale (NRS), Short-Form McGill Pain Questionnaire (SF-MPQ), Hamilton rating scale for Depression and Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) were administered.Results: The BMS patients presented statistically significant higher scores on the ARWMCs compared to the controls, especially in the right frontal, left frontal, right parietal-occipital, left parietal-occipital, right temporal and left temporal lobes (p-values: <0.001, <0.001, 0.005, 0.002, 0.009, 0.002, and <0.001, respectively). Age, a lower educational level, unemployment, essential hypertension, and hypercholesterolemia were correlated to a higher total score on the ARWMCs (p-values: <0.001, 0.016, 0.014, 0.001, and 0.039, respectively). No correlation was found with the blood biomarkers, NRS, SF-MPQ, HAM-A, HAM-D, PSQI, and ESS.Conclusion: Patients with BMS showed a higher frequency of WMHs of the brain as suggested by the higher ARWCs scores compared with the normal aging of the healthy subjects. These findings could have a role in the pathophysiology of the disease and potentially affect and enhance pain perception.

Chronic neuropathic pain (CNP) is a disabling medical condition that impairs the health-related quality-of-life of affected patients. A high prevalence of anxiety, depression, sleep disturbance and cognitive impairment has frequently been reported in association with CNP, making the management of this disease complex and often multidisciplinary. Dual-acting agents such as selective serotonin and noradrenalin reuptake inhibitors (SNRIs) are considered particularly useful in the modulation of pain and in treatment of the mood disorders frequently associated with CNP. Recent evidence suggests that the top-down inhibitory control of pain involves the engagement and enhancement of descending endogenous opioidergic, cannabinoid and serotonergic systems, with the effect of serotonin being particularly related to the receptor subtypes that are preferentially activated; indeed serotonin induces analgesia via activation of 5-HT7 receptors and hyperalgesia via activation of 5-HT3 receptors. Vortioxetine (VO) is a novel multimodal serotonergic antidepressant with a unique mechanism of action. It has been demonstrated recently in experimental and clinical studies to have efficacy on pain hypersensitivity and on mood disorders. This drug inhibits the serotonin transporter with a high affinity, antagonises the 5-HT3, 5-HT1D and 5HT7 serotonin receptors, and activates the 5-HT1A and 5-HT1B receptors. In clinical studies, VO has proved effective at a dose of 10–20 mg/daily in short- and long-term treatment of patients with chronic orofacial pain, demonstrating a higher rate of clinical response and remission, a better acceptability, safety rate and tolerability, and a lower latency of action compared with other antidepressants. In the light of these recent findings, VO may be considered as a new pharmacological treatment also in relation to various types of CNP, particularly in elderly patients with concomitant mood disorders and cognitive impairment. The purpose of this review is to provide an up-to-date overview of the pharmacology and clinical applications of VO and to highlight its potential therapeutic properties and advantages in the management of CNP.