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Pathophysiological hypotheses of burning mouth syndrome. HRV: heart rate variability; HPA axis: hypothalamic-pituitary-adrenal axis; EGMt: electrogustometric thresholds; NGF: nerve growth factor; TRPV1: transient receptor potential vanilloid type 1. Author Contributions: Conceptualization: L.M.; methodology: L.M. and M.O.; bibliographical research: M.O.; analysis of papers: M.O.; selection of papers L.M. and M.O.; writing-original draft preparation: M.O.; review and editing: L.M.; supervision: L.M. Both authors have read and agreed to the published version of the manuscript.
Source publication
Abstract: The pathophysiology of primary burning mouth syndrome (BMS) has been extensively debated but is poorly understood despite a large number of hypotheses attempting to explain its etiopathogenic mechanisms. The aim of the present work was to systematically review papers that could provide arguments in favour of the neuropathic and psychogeni...
Context in source publication
Context 1
... neurogenic and psychogenic components may be involved in the pathophysiology of BMS (Figure 2). The International Association for the Study of Pain (IASP) recently defined three different pains: nociceptive pain, "pain that arises from actual or threatened damage to non-neural tissue and is due to the activation of nociceptors"; neuropathic pain, "pain caused by a lesion or disease of the somatosensory nervous system"; and nociplastic pain, "pain that arises from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors and no evidence of a disease or lesion of the somatosensory system causing the pain" [143- 145]. ...
Citations
... Evidence suggests that the mechanism of BMS is neuropathic in nature [5]. In the neuropathic pathophysiology theory, sensory dysfunction is associated with small and/or large fiber neuropathy where there is axonal degeneration of epithelial and subpapillary nerve fibers in the affected epithelium of the oral mucosa [6]. There is also an abnormal interaction between the sensory functions of facial and trigeminal nerves. ...
Objective
The aim of this retrospective study was to evaluate the effectiveness and safety of topical gabapentin solution (250 mg/mL) for the management of burning mouth syndrome (BMS).
Study design
A retrospective chart review was conducted of all patients diagnosed with BMS and managed with gabapentin 250 mg/mL solution (swish and spit) between January 2021 and October 2022. Patient-reported outcomes included changes in burning score ranked on a 10-point numeric rating scale (NRS) and reported adverse drug reactions (ADR). Wilcoxon signed-rank test was used to assess differences in the oral burning score ranked on a NRS (0–10) between the baseline visit and the second visit.
Results
A total of 19 patients (68.4% females) with BMS were included and evaluated for follow-up at a median of 86 days (range: 29–195). Overall, patients reported a median 2-point burning decrease on a 0–10 NRS between the baseline visit and the second visit (p < 0.01). ADRs were reported by 3 patients (15.8%).
Conclusion
Although this was a small retrospective study, BMS management with topical gabapentin (250 mg/mL) appears to be effective and well-tolerated. Future randomized prospective studies are needed to verify these preliminary findings.
... Earlier tongue biopsy analysis showed that the density of intraepidermal and epithelial nerve fibers in BMS patients was significantly lower than that in healthy subjects [12][13][14]. In fact, neurophysiological, psychophysical and functional imaging studies have shown pathophysiological alterations at different levels of the neural axis, and BMS is currently believed to be neuropathic pain affecting the central and peripheral nervous systems [15]. Studying the clinical features and sensory changes associated with BMS might help in BMS management and treatment. ...
Background
Burning mouth syndrome (BMS) is an oral-facial pain disorder involving the central and peripheral nervous systems, but the evidence for altered pain sensitivity remains inconclusive. The aim of this study was to investigate pain sensitivity and oral health-related quality of life (OHRQoL) in patients with BMS and to assess the relationship between them.
Methods
Fifty Chinese patients with BMS (57.82 ± 11.2 years) and fifty age- and gender-matched healthy subjects (55.64 ± 10.1 years) participated in the study. The Pain Sensitivity Questionnaire (PSQ) was used to assess participants’ pain sensitivity. The Oral Health Impact Profile (OHIP-14) was used to evaluate participants’ OHRQoL.
Results
The PSQ total score (p = 0.009), the PSQ minor score (p = 0.003) and the OHIP-14 score (p<0.05) of patients with BMS were significantly higher than those of the healthy subjects. Simple linear regression showed that the PSQ minor score was significantly associated with the OHIP-14 score in patients with BMS (β = 0.338, p = 0.016).
Conclusion
Patients with BMS have higher pain sensitivity than healthy subjects. Reducing pain sensitivity might help to improve the quality of life of patients with BMS.
... Previous research has demonstrated a relationship between BMS and the central and/or peripheral neuropathic and psychogenic contributors [20,21]. One investigation that may shed some light on the cerebral etiology of BMS is functional brain imaging [19]. ...
Background and Objectives: Noncommunicable diseases (NCDs) are a group of non-transmissible conditions that tend to be of long duration and are the result of a combination of genetic, physiological, environmental, and behavioral factors. Although an association between oral disorders and NCDs has been suggested, the relationship between Burning Mouth Syndrome (BMS) and NCDs and their associated risk factors has not been deeply investigated. In this study, we aim to identify associations between BMS and NCDs in the Romanian population. Materials and Methods: Ninety-nine BMS patients and 88 age-matched controls (aged 50 and over) were clinically evaluated for the presence of eight noncommunicable diseases (NCDs) and their most common risk factors, including hypertension, dyslipidemia, smoking, and obesity. Results: The results of our study showed that the BMS in the Romanian population seems to be significantly associated with cardiovascular diseases (CVDs) (p < 0.001) and two of their risk factors, hypertension (p < 0.001) and dyslipidemia (p < 0.001). Moreover, evaluating the Framingham Risk Score (FRS) in the individuals not affected by CVDs (73 CTRL and 38 BMS), we found that 13.2% of BMS patients reported a moderate risk of developing CVDs in ten years, compared to the controls, all of whom presented a low risk (p = 0.002). Conclusions: Our findings suggest that a multidisciplinary clinical approach, which also includes a cardiovascular evaluation, is essential for the successful management of BMS. Moreover, these data highlighted the importance of introducing an integrated strategy for the prevention and care of NCDs in BMS patients.
... Moreover, multidisciplinary therapy may be more effective in enhancing the quality of life than the current intervention method, which is excessively homogenous [60]. Therefore, multidisciplinary intervention designs, such as LLLT combined with functional movement, acupuncture, meditation, and psychological support, are recommended for future research on effectively improving the quality of life among patients with BMS [60][61][62]. ...
Background
Burning mouth syndrome (BMS) is a complex chronic pain disorder that significantly impairs patients' quality of life. Low-level laser therapy (LLLT) uses infrared or near-infrared light to produce analgesic, anti-inflammatory, and biological stimulation effects. The aim of this systematic review is to evaluate the effect of LLLT on burning pain, quality of life, and negative emotions in patients with BMS.
Methods
The PubMed, Embase, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Cochrane Library, Web of Science, and Scopus databases were searched up January 2023 to identify relevant articles. All randomized controlled trials that were published in English and examined the use of LLLT treatment for BMS were included. The methodological quality of the included trials was assessed using the Cochrane risk of bias tool for randomized controlled trials (RCTs). A meta-analysis was performed to evaluate burning pain, quality of life, and negative emotions. Sensitivity, subgroup, and funnel plot analyses were also carried out.
Results
Fourteen RCTs involving a total of 550 patients with BMS met the inclusion criteria. The results showed that LLLT (measured by the Visual Analog Scale; SMD: -0.87, 95% CI: -1.29 to -0.45, P < 0.001) was more effective for reducing burning pain than placebo LLLT or clonazepam. LLLT improved quality of life (evaluated by the Oral Health Impact Profile-14; SMD: 0.01, 95% CI: -0.58 to 0.60, P = 0.97) and negative emotions (evaluated by the Hospital Anxiety and Depression Scale; SMD: -0.12, 95% CI: -0.54 to 0.30, P = 0.59), but these effects were not statistically significant.
Conclusions
The meta-analysis revealed that LLLT may be an effective therapy for improving burning pain in patients with BMS, and producing a positive influence on quality of life and negative emotions. A long-term course of intervention, a larger sample size, and a multidisciplinary intervention design are urgently needed in future research.
Trial registration
PROSPERO registration number: CRD42022308770.
... 22,23 Finally, there are also some specific psychodermatological disorders where the role of psychological/psychiatric disorders is huge in the pathophysiology of skin lesions (such as dermatitis artefacta/facticious disorder or skin picking syndrome) [24][25][26] or sensory skin disorders (such as burning mouth syndrome) and persistent delusional disease (such as delusional infestation). 11,[27][28][29] The psychodermatological approach aims to identify such associations between psychological factors and signs of skin conditions in patients with skin diseases in order to offer certain psychological or psychopharmacological therapies or interventions to these patients. Interventions comprise pharmacological interventions and/or psychological interventions, for example cognitive behavioural therapies, psychodynamic therapies, mindfulness-based interventions, stress management and relaxation trainings as well as family systemic therapies [30][31][32][33] in addition to appropriate and contemporaneous management of any cutaneous disease. ...
Psychodermatology is a subspecialty of dermatology that is of increasing interest to dermatologists and patients. The case for the provision of at least regional psychodermatology services across Europe is robust. Psychodermatology services have been shown to have better, quicker and more cost-efficient clinical outcomes for patients with psychodermatological conditions. Despite this, psychodermatology services are not uniformly available across Europe. In fact many countries have yet to establish dedicated psychodermatology services. In other countries psychodermatology services are in development. Even in countries where psychodermatolgy units have been established, the services are not available across the whole country. This is especially true for the provision of paediatric psychodermatology services. Also whilst most states across Europe are keen to develop psychodermatology services, the rate at which this development is being implemented is very slow. Our paper maps the current provision of psychodermatology services across Europe and indicates that there is still very much more work to be done in order to develop the comprehensive psychodermatology services across Europe, which are so crucial for our patients.
... According to our previous work on burning mouth syndrome, we hypothesised that neuropathic and psychogenic factors could be frequently associated. 18 The main objective of the present work, which was based on questionnaires, was to highlight the differences and the potential common characteristics between PP and NP to improve the differential diagnosis between these two pathologies. Secondary objectives were to describe the psychogenic and neurogenic characteristics of PP and NP to improve the understanding of the mechanism and, therefore, their management. ...
Abstract
Background: The causes of pruritus are multiple and commonly classified into six different categories: dermatological, systemic, neuropathic, psy- chogenic, mixed and idiopathic. In clinical practice, psychogenic and neurogenic mechanisms tend to be separated in the etiological diagnosis of neuropathic or psychogenic disorders; nevertheless, studies investigating the respective psychogenic and neurogenic components are lacking. Objective: The main objective of this work was to highlight the differences and potential common characteristics between psychogenic pruritus and neuropathic pruritus.
Methods: This study was a noninterventional single‐centre prospective assay. Patients with neuropathic (NP) or psychogenic (PP) pruritus were proposed to participate. The psychogenic and neurogenic components of pruritus in these patients were evaluated using six validated questionnaires or criteria, namely, the diagnosis criteria of psychogenic pruritus, the NP5 questionnaire, the Brest Pruritus Qualitative Assessment Questionnaire, Hospital Anxiety and Depression Scale, Toronto Alexithymia Scale, and DN4i.
Results: Twenty‐five patients with NP and 15 with PP were included. A difference between the two groups was observed for NP5, with mean scores of 2.8 � 0.9 and 1.4 � 1 for the NP and PP groups, respectively (p < 0.0001). For depression, the average score was 3.5 � 3.9 for the NP group and 7.5 � 5.1 for the PP group (p < 0.02).
Conclusion: While neuropathic and psychogenic disorders are different diagnoses, neuropathic and psychogenic components may exist simulta- neously in patients with NP or PP.
... In accordance with the biopsychosocial model of chronic pain as a multidimensional phenomenon, in which psychological, cognitive, and emotional factors, as well as multimorbidity, may play a role in pain [8], depressive and anxiety disorders are the most common and the most frequently investigated psychiatric conditions in BMS patients [9,10]. While there are some systematic reviews and meta-analyses investigating the relationship of depressive and anxiety disorders in BMS patients without selection for age groups [11,12], a subgroup analysis by age in a large and recent meta-analysis showed the prevalence was higher for individuals over 50 years (3.31%) than under 50 years (1.92%) [13]. Therefore, the objective of the present systematic review was to investigate the relationship of BMS with depressive and anxiety disorders in middle-aged and older adults. ...
... This study confirmed the present findings in middle and older age, suggesting that among BMS patients, anxiety and depression were the most common and most frequently studied psychiatric disorders [11]. The present findings were confirmed also by a very recent systematic review without selection for age groups showing a link of BMS with psychiatric disorders, particularly anxiety and/or depressive symptoms [12]. ...
Background:
Burning Mouth Syndrome (BMS) is an idiopathic condition mainly affecting middle-aged and older individuals with hormonal disturbances or psychiatric disorders and is characterized by chronic pain. The etiopathogenesis of this multifactorial syndrome is largely unknown. The objective of the present systematic review was therefore to evaluate the relationship of BMS with depressive and anxiety disorders in middle-aged and older individuals.
Methods:
We selected studies evaluating BMS and depressive and anxiety disorders assessed with validated tools, published from their inception up to April 2023, using PubMed, MEDLINE, EMBASE, Scopus, Ovid, and Google Scholar databases and adhering to the PRISMA 2020 guidelines/PRISMA 2020 27-item checklist. This study is registered on PROSPERO (CRD42023409595). The National Institutes of Health Quality Assessment Toolkits for Observational Cohort and Cross-Sectional Studies were used to examine the risk of bias.
Results:
Two independent investigators rated 4322 records against the primary endpoint and found 7 records meeting the eligibility requirements. Anxiety disorders were found to be the most common psychiatric disorders related to BMS (63.7%), followed by depressive disorders (36.3%). We found a moderate association of BMS with anxiety disorders, with multiple studies included (n = 7). Moreover, we found a low association of BMS with depressive disorders (included studies, n = 4). The role of pain appeared to be controversial in explaining these associations.
Conclusions:
In middle-aged and older subjects, anxiety and depressive disorders may be potentially related to the development of BMS. Furthermore, also in these age groups, females showed higher risk of developing BMS than males, even when taking into account multimorbidity such as sleep disorders, personality traits, and biopsychosocial changes as suggested by study-specific findings.
... Chronic headaches often have features of NcplP and can be classified as chronic primary headaches, orofacial pain, tension-type headaches, and migraines [14,15,19,46,53,83]. Orofacial pain with the characteristic symptoms of NcplP can be a part of temporomandibular joint dysfunction and burning mouth syndrome [8,15,19,22,41,53,[82][83][84]. Furthermore, shoulder and neck pain can develop in patients with primary myofascial pain or in breast cancer survivors. ...
Nociplastic pain is a recently distinguished type of pain, distinct from neuropathic and nociceptive pain, and is well described in the literature. It is often mistaken for central sensitization. Pathophysiology has not been clearly established with regard to alteration of the concentration of spinal fluid elements, the structure of the white and gray matter of the brain, and psychological aspects. Many different diagnostic tools, i.e., the painDETECT and Douleur Neuropathique 4 questionnaires, have been developed to diagnose neuropathic pain, but they can also be applied for nociplastic pain; however, more standardized instruments are still needed in order to assess its occurrence and clinical presentation. Numerous studies have shown that nociplastic pain is present in many different diseases such as fibromyalgia, complex regional pain syndrome type 1, and irritable bowel syndrome. Current pharmacological and nonpharmacological treatments for nociceptive and neuropathic pain are not entirely suitable for treating nociplastic pain. There is an ongoing effort to establish the most efficient way to manage it. The significance of this field has led to several clinical trials being carried out in a short time. The aim of this narrative review was to discuss the currently available evidence on pathophysiology, associated diseases, treatment possibilities, and clinical trials. It is important that physicians widely discuss and acknowledge this relatively new concept in order to provide optimized pain control for patients.
... Another classification, based on the concept that BMS is a neuropathic disorder, identifies two subtypes of this disease: a subgroup characterized by peripheral small diameter fiber neuropathy of the oral mucosa and a subgroup characterized by central neuropathy. In some patients, the presence of both subtypes may occur (Orliaguet and Misery, 2021;van der Waal, 2021). ...
Burning Mouth Syndrome (BMS) is a chronic condition characterized by a burning sensation in the oral mucosa, lasting more than 2 hours daily for more than 3 months, without clinical and/or laboratory evidence. BMS is often comorbid with mood, and psychiatric disorders, and a complex pathophysiology and interaction between impairments in nociceptive processing and psychologic function is occurring. In this work, we aimed to define the neuropsychological profile specific for BMS patients for a better management of this complex disease. We conducted a case–control study comparing 120 BMS patients and 110 non-BMS individuals (CTRL). Sociodemographic data and lifestyle habits, were collected, along with data regarding quality of life (SF-36 scale), stress (PSS), depression and anxiety (MADRS and HADS scales), sleep quality (PSQI scale), and cognitive functions (MoCA, SVF and PVF tests). The statistical analysis revealed a lower general quality of life (p < 0.001), worse sleep quality (p < 0.001) in BMS patients than CTRL. The BMS patients also displayed a higher prevalence of mild depressive symptoms than CTRL applying the MADRS (p < 0.001) and HADS-Depression scales (p = 0.001), whereas no differences in anxiety symptoms were found between the two groups (p = 0.174). Moreover, reduced scores semantic and phonemic verbal fluency tests (p < 0.05) were found, but no change in cognition was observed through MoCA (p = 0.551). Our results highlight that synergy between dentistry and neuropsychiatric assessment is essential for a successful management of BMS.
... Central neuropathic mechanisms in BMS are associated with hypofunction of the central dopaminergic system in the basal ganglia and decreased endogenous inhibitory control [2,4,11]. Patients of BMS with central neuropathic mechanisms often seem to have associated psychiatric disorders such as depression and anxiety [12,13]. ...
