WWOM VII: Effectiveness of systemic pharmacotherapeutic interventions in the management of BMS: A systematic review and meta-analysis.

OBJECTIVES: To determine the effectiveness of systemic pharmacotherapeutic interventions compared to placebo in burning mouth syndrome (BMS) randomized controlled trials (RCTs) based on the core outcome domains recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT). METHODS: A systematic literature review of RCTs, concerning systemic pharmacotherapeutic interventions for BMS, published from January 1994 through October 2019, and meta-analysis was performed. RESULTS: Fourteen RCTs (n = 734 participants) were included. Of those, nine were eligible for the quantitative assessment due to the availability/homogeneity of data for at least one of the IMMPACT domains. Pain intensity was the only domain reported in all RCTs. Weighted mean changes in pain intensity, based on visual analogue scale (ΔVAS), were reported in three RCTs at 6 ± 2 weeks and only one RCT at 10+ weeks follow-ups. Quantitative assessment, based on ΔVAS, yielded very low evidence for the effectiveness of alpha-lipoic acid and clonazepam, low evidence for effectiveness of trazodone and melatonin, and moderate evidence for herbal compounds. CONCLUSIONS: Based on the RCTs studied, variable levels of evidence exist that suggest that select pharmacological interventions are associated with improved symptoms. However, the underreporting of IMMPACT domains in BMS RCTs restricts the multidimensional assessment of systemic interventions outcomes. Standardized outcome measures need to be applied to future RCTs to improve understanding of intervention outcomes.

WWOM VII: Effectiveness of topical interventions in the management of burning mouth syndrome: A systematic review.

OBJECTIVES: To assess the effectiveness of topical interventions in the management of burning mouth syndrome (BMS), based on the core outcome domains recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT). METHODS: A systematic literature review of RCTs on topical interventions for the management of BMS, published in PubMed, Web of Science, PsycInfo, Cochrane Database/Central, and Google Scholar through May 2021 was performed. RESULTS: Eight RCTs (n = 358 study participants) were included in this study. Due to underreporting of IMMPACT domains, publication bias, high degree of heterogeneity between studies, meta-analysis was not undertaken. Based on changes in visual analogue pain scores (ΔVAS), the most reported outcome, the effectiveness of the topical interventions was demonstrated; however, it is low level of evidence. CONCLUSIONS: High levels of variability (interventions, outcomes, outcome measurement tools, and intervention effects evaluated), heterogeneity, publication bias, and underreporting of IMMPACT domains were observed across the RCTs. This systematic review highlights the need for application of standardized outcome measures to future RCTs. At the present time, there is lack of moderate-strong evidence on short- and long-term outcomes to support or refute the use of any particular topical intervention in managing BMS. Future RCTs with standardized outcome measures are needed.

Genetic variation in catechol-O-methyltransferase is associated with individual differences in conditioned pain modulation in healthy subjects.

BACKGROUND: Genetic variation in the catechol-O-methyltransferase (COMT) gene is associated with sensitivity to both acute experimental pain and chronic pain conditions. Four single nucleotide polymorphisms (SNPs) have traditionally been used to infer three common haplotypes designated as low, average and high pain sensitivity and are reported to affect both COMT enzymatic activity and pain sensitivity. One mechanism that may partly explain individual differences in sensitivity to pain is conditioned pain modulation (CPM). We hypothesized that variation in CPM may have a genetic basis. METHODS: We evaluated CPM in 77 healthy pain-free Caucasian subjects by applying repeated mechanical stimuli to the dominant forearm using 26-g von Frey filament as the test stimulus with immersion of the non-dominant hand in hot water as the conditioning stimulus. We assayed COMT SNP genotypes by the TaqMan method using DNA extracted from saliva. RESULTS: SNP rs4680 (val158 met) was not associated with individual differences in CPM. However, CPM was associated with COMT low pain sensitivity haplotypes under an additive model (p = 0.004) and the effect was independent of gender. CONCLUSIONS: We show that, although four SNPs are used to infer COMT haplotypes, the low pain sensitivity haplotype is determined by SNP rs6269 (located in the 5' regulatory region of COMT), suggesting that inherited variation in gene expression may underlie individual differences in pain modulation. Analysis of 13 global populations revealed that the COMT low pain sensitivity haplotype varies in frequency from 13% to 44% and showed that two SNPs are sufficient to distinguish all COMT haplotypes in most populations.

Developing a research diagnostic criteria for burning mouth syndrome: Results from an international Delphi process.

OBJECTIVE: To develop a beta version of a preliminary set of empirically derived research diagnostic criteria (RDC) for burning mouth syndrome (BMS) through expert consensus, which can then be taken into a test period before publication of a final RDC/BMS. DESIGN: A 6 round Delphi process with twelve experts in the field of BMS was used. The first round formed a focus group during which the purpose of the RDC and the definition of BMS was agreed upon, as well as the structure and contents. The remaining rounds were carried out virtually via email to achieve a consensus of the beta version of the RDC/BMS. RESULTS: The definition of BMS was agreed to be 'an intraoral burning or dysaesthetic sensation, recurring daily for more than 2 hours per day over more than 3 months, without evident causative lesions on clinical examination and investigation'. The RDC was based upon the already developed and validated RDC/TMD and formed three main parts: patient self-report; examination; and psychosocial self-report. A fourth additional part was also developed listing aspirational biomarkers which could be used as part of the BMS diagnosis where available, or to inform future research. CONCLUSION: This Delphi process has created a beta version of an RDC for use with BMS. This will allow future clinical research within BMS to be carried out to a higher standard, ensuring only patients with true BMS are included. Further validation studies will be required alongside refinement of the RDC as trialling progresses.

World Workshop on Oral Medicine VII: Burning mouth syndrome: A systematic review of disease definitions and diagnostic criteria utilized in randomized clinical trials.

OBJECTIVE: To conduct a systematic review analyzing disease definitions and diagnostic criteria used in randomized controlled trials (RCTs) involving burning mouth syndrome (BMS). METHODS: A systematic search conducted in PubMed, Web of Science, PsycINFO, Cochrane Database/Cochrane Central, and Google Scholar that included RCTs on BMS published between 1994 and 2017 was performed. RESULTS: Considerable variability in BMS disease definitions and diagnostic criteria used created substantial heterogeneity in the selection of participants and weakened the rigor of the 36 RCTs identified. The analyzed RCTs routinely under-reported the methods used to rule in or out study participants and the number of individuals excluded from BMS RCTs. CONCLUSIONS: Our findings indicate that a large proportion of participants enrolled in these studies may have had an underlying condition that could have explained their BMS symptoms. Thus, outcomes of therapeutic interventions from these BMS RCTs should be interpreted with caution due to heterogeneous disease definitions and diagnostic criteria. In order to improve the quality of clinical trials, future research should focus on establishing consensus for a single definition of BMS that includes specific inclusion and exclusion criteria that should be used to select study participants for clinical trials.

World Workshop in Oral Medicine VII: Reporting of IMMPACT-recommended outcome domains in randomized controlled trials of burning mouth syndrome: A systematic review.

OBJECTIVES: To determine the frequency of use of the core outcome domains published by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) in burning mouth syndrome (BMS) randomized controlled trials (RCTs). METHODS: This systematic review, conducted as part of the World Workshop on Oral Medicine VII (WWOM VII), was performed by searching the literature for studies published in PubMed, Web of Science, PsycINFO, Cochrane Database/Cochrane Central, and Google Scholar from January 1994 (when the first BMS definition came out) through October 2017. RESULTS: A total of 36 RCTs (n = 2,175 study participants) were included and analyzed. The overall reporting of the IMMPACT core and supplemental outcome domains was low even after the publication of the IMMPACT consensus papers in 2003 and 2005 (mean before IMMPACT consensus publication = 2.6 out of 6; mean after IMMPACT publication = 3.8 out of 6). Use of validated assessment tools recommended by the IMMPACT consensus was scarce (1.9 out of 6). None of the RCTs reviewed cited the IMMPACT consensus papers. CONCLUSIONS: The underreporting of IMMPACT outcome domains in BMS RCTs is significant. Raising awareness regarding the existence of standardized outcome domains in chronic pain research is essential to ensure more accurate, comparable, and consistent interpretation of RCT findings that can be clinically translatable.

Burning mouth syndrome: Current concepts.

Burning mouth syndrome (BMS) is a chronic pain condition. It has been described by the International Headache Society as "an intra-oral burning or dysesthetic sensation, recurring daily for more than 2 h/day for more than 3 months, without clinically evident causative lesions." BMS is frequently seen in women in the peri-menopausal and menopausal age group in an average female/male ratio of 7:1. The site most commonly affected is the anterior two-thirds of the tongue. The patient may also report taste alterations and oral dryness along with the burning. The etiopathogenesis is complex and is not well-comprehended. The more accepted theories point toward a neuropathic etiology, but the gustatory system has also been implicated in this condition. BMS is frequently mismanaged, partly because it is not well-known among healthcare providers. Diagnosis of BMS is made after other local and systemic causes of burning have been ruled out as then; the oral burning is the disease itself. The management of BMS still remains a challenge. Benzodiazepines have been used in clinical practice as the first-line medication in the pharmacological management of BMS. Nonpharmacological management includes cognitive behavioral therapy and complementary and alternative medicine (CAM). The aim of this review is to familiarize healthcare providers with the diagnosis, pathogenesis, and general characteristics of primary BMS while updating them with the current treatment options to better manage this group of patients.

Combined palliative and anti-inflammatory medications as treatment of temporomandibular joint disc displacement without reduction: a systematic review.

The aim of this study was to evaluate the efficacy of self-care combined with anti-inflammatory medications in the treatment of temporomandibular joint (TMJ) pain associated with disc displacement without reduction (DDWOR). A systematic review of randomized clinical trials was done by the authors. The databases searched were Medline (1966 to July 2012); EMBASE (1980 to July 2012); and LILACS (from 1982 to July 2012). The review authors independently assessed trials for eligibility and methodological quality and also extracted all data. The data was double-checked for accuracy. There was no language restriction in the searches of EMBASE, PubMed, and LILACS databases, or in the manual search. The risk of bias and the heterogeneity of the studies taken into consideration were assessed. Two studies, randomizing 175 patients, were included in this review. The first study (n = 106) compared the following interventions: medical treatment, rehabilitation, arthroscopic surgery with postoperative rehabilitation, or arthroplastic surgery with post-operative rehabilitation. The second study (n = 69) compared the use of nonsteroidal anti-inflammatory medications and self-care instructions, nonsteroidal anti-inflammatory medications, occlusal splint, and mobilization therapy. The third group received no treatment; patients were only informed of their prognosis. There is no sufficient evidence regarding efficacy and safety of the palliative treatments associated with anti-inflammatory versus other treatments, or absence of treatment on pain reduction in patients with TMJ DDWOR.

Temporomandibular Joint Disorders and the Eating Experience.

Temporomandibular joint disorder (TMD) is a chronic disorder that significantly affects oral function. It can affect appetite and the mechanical components involved with eating, including mandibular opening, biting, chewing, and even swallowing. Thus, dietary intake and, subsequently, nutrition status are affected. The functional challenges presented by the disorder affect eating-related quality of life and can affect food choices and diet quality and composition. This article addresses disorder-related factors affecting the eating experience of adults with TMDs and approaches to diet management.

Burning mouth syndrome.

According to the International Association for the Study of Pain, burning mouth Syndrome (BMS) is defined as a burning pain in the tongue or other oral mucous membrane in the absence of clinical signs or laboratory findings. The etiology is unknown and presents a challenge for both researchers and clinicians. The management of BMS is still not satisfactory. The prognosis is poor and the burning sensation can last for many years causing a dramatic impact on the patient's quality of life. It is important to distinguish between true BMS and symptomatic burning sensation which occurs when the burning sensation is secondary to a local or systemic pathologic condition. Currently, there are no defined diagnostic criteria for BMS. A diagnosis is usually reached by exclusion of other diseases. This may lead to misdiagnoses, presenting an obstacle to successful treatment.

Sensory Changes Related to Dental Implant Placement: A Scoping Review.

AIMS: To perform a scoping review of the literature to elucidate the occurrence of nerve damage related to dental implant placement and the factors causing the sensory changes. METHODS: An extensive electronic search was conducted using the Cochrane Library, Medline via Ovid, PubMed, Wiley Online, Science Direct, CINAHL, and the Google Scholar databases from the year 1950 to 2020. RESULTS: The search resulted in 1,067 articles, out of which 76 were selected for this review. The articles were categorized as literature review articles, retrospective studies, prospective studies, and case series/case reports. Altogether, 2,526 subjects were assessed retrospectively, with 5.27% transient and 1.39% persistent sensory changes, and a cohort of 2,750 subjects were followed prospectively, with 6.22% transient and 1.31% persistent sensory changes. A total of 336 subjects were enrolled in various case reports and case series, with 5.95% transient sensory changes and 84.52% persistent neurosensory changes. The articles included were not of high quality and have variations in their study designs and reporting procedures, with limited sensory change data to include in this study. CONCLUSION: After surgical placement of dental implants in 5,612 patients, the incidence of transient sensory changes was 5.63%, and the incidence of persistent sensory changes was 6.33%. Factors affecting the incidence were: mandibular location of the implant, with the inferior alveolar nerve as the most commonly affected nerve. The common symptoms reported were paresthesia and dysesthesia. Age and gender were among other factors, for which data were not available in all the articles.

Consensus agreement to rename burning mouth syndrome and improve International Classification of Diseases-11 disease criteria: an international Delphi study.

ABSTRACT: The International Classification of Diseases (ICD-11) proposes revisions in the nomenclature, disease definition, and diagnostic criteria for "burning mouth syndrome" (BMS). This process could benefit from additional systematically collected expert input. Thus, the purpose of this study was to use the Delphi method to (1) determine whether revision in nomenclature and alternative names for "BMS" are warranted and (2) identify areas of consensus among experts for changes to the disease description and proposed diagnostic criteria of "BMS," as described in the ICD-11 (World Health Organization). From 31 international invited experts, 23 who expressed interest were sent the survey. The study used 4 iterative surveys, each with a response rate of ≥82%. Consensus was predefined as 70% of participants in agreement. Data were summarized using both descriptive statistics and qualitative thematic analysis. Consensus indicated that BMS should not be classified as a syndrome and recommended instead renaming to "burning mouth disorder." Consensus included deletion of 2 diagnostic criteria: (1) emotional distress or functional disability and (2) the number of hours symptoms occur per day. Additional items that reached consensus clarified the disease definition and proposed more separate diagnostic criteria, including a list of local and systemic factors to evaluate as potential secondary causes of oral burning. Experts in this study recommended and came to consensus on select revisions to the proposed ICD-11 BMS nomenclature, diagnostic criteria, and disease definition. The revisions recommended have the potential to improve clarity, consistency, and accuracy of diagnosis for this disorder.

An improved cost-effective, reproducible method for evaluation of bone loss in a rodent model.

AIM: This study was designed to investigate the utility of two "new" definitions for assessment of bone loss in a rodent model of periodontitis. MATERIAL AND METHODS: Eighteen rats were divided into three groups. Group 1 was infected by Aggregatibacter actinomycetemcomitans (Aa), group 2 was infected with an Aa leukotoxin knock-out, and group 3 received no Aa (controls). Microbial sampling and antibody titres were determined. Initially, two examiners measured the distance from the cemento-enamel-junction to alveolar bone crest using the three following methods; (1) total area of bone loss by radiograph, (2) linear bone loss by radiograph, (3) a direct visual measurement (DVM) of horizontal bone loss. Two "new" definitions were adopted; (1) any site in infected animals showing bone loss >2 standard deviations above the mean seen at that site in control animals was recorded as bone loss, (2) any animal with two or more sites in any quadrant affected by bone loss was considered as diseased. RESULTS: Using the "new" definitions both evaluators independently found that infected animals had significantly more disease than controls (DVM system; p<0.05). CONCLUSIONS: The DVM method provides a simple, cost effective, and reproducible method for studying periodontal disease in rodents.

The Effect of Nonstrenuous Aerobic Exercise in Patients with Chronic Masticatory Myalgia.

AIMS: To evaluate the effect of nonstrenuous aerobic exercise on chronic masticatory myalgia (CMM) patients and healthy controls (HC) by means of mechanical temporal summation (TS) and response to mechanical stimulation (RMS) performed on the dominant forearm. METHODS: A total of 30 patients diagnosed with CMM and 30 pain-free HCs were first evaluated for maximum number of steps (MNS) on a stepper machine for 1 minute. Additionally, they completed the Generalized Anxiety Disorder (GAD-7), Graded Chronic Pain Scale (GCPS), and Jaw Functional Limitation Scale (JFL) questionnaires. On the second visit, RMS, mechanical TS, exercise-induced hypoalgesia (EIH), blood pressure, pulse pressure, and heart rate were assessed prior to and immediately, 5, 15, and 30 minutes following 5 minutes of stepper exercise at 50% MNS. RESULTS: Compared to HCs, CMM patients demonstrated increased mechanical TS and less efficient EIH. Mechanical TS scores were reduced in both groups; however, the HC reduction was more robust and persistent. CMM patients demonstrated a delayed reduction in RMS following exercise in contrast to an immediate reduction in HCs. GAD-7, GCPS, and JFL scores for CMM patients were higher than for HCs and were associated with baseline pain intensity but not with EIH or TS. CONCLUSION: These findings suggest that, compared to HC, CMM patients' pain modulation is both suppressed and has a different effect duration and timing pattern. Further research should explore the mechanisms and clinical relevance of the delayed hypoalgesia and the inhibitory effect on TS induced by nonstrenuous aerobic exercise in CMM patients.

Orbital pseudotumor presenting as a temporomandibular disorder: A case report and review of literature.

BACKGROUND AND OVERVIEW: Orofacial pain has multifactorial causes and is often a diagnostic challenge. Misdiagnosis can result in morbidity or mortality due to misdirected and inappropriate treatment. A delay of necessary treatment, in cases of ominous illnesses, may result in its perpetuation or progression. The authors present a case report that illustrates these possibilities. CASE DESCRIPTION: This case report describes a 36-year-old woman with the chief symptom of painless, limited mandibular movement. She also reported restricted movement of the left eye. She was previously diagnosed and treated for a traumatic right inferior alveolar nerve neuropathy, migraine, myofascial pain, and bilateral temporomandibular joint disk displacement with minimal benefit. Eventually she sought an orofacial pain evaluation, presuming her problems were related to a temporomandibular disorder. A complete history and comprehensive clinical evaluation including a cranial nerve screening evaluation, intraoral and extraoral examinations, an evaluation of the masticatory system, and dental radiographs were performed. The cranial nerve screening examination found painful, restricted eye movements. Magnetic resonance revealed a large, soft tissue mass in the inferolateral wall of the left orbit with soft tissue components in the infratemporal fossa and pterygoid space, involving the lateral pterygoid muscle and insertion of the temporalis muscle. The patient was referred to appropriate medical specialties and the diagnosis of orbital pseudotumor was confirmed and the patient was treated appropriately. CONCLUSIONS AND PRACTICAL IMPLICATIONS: The case emphasizes the importance of a comprehensive evaluation of a patient with preexisting orofacial pain when new symptoms arise or if there is a change in existing symptoms.

Primary burning mouth syndrome: Literature review and preliminary findings suggesting possible association with pain modulation.

Primary burning mouth syndrome (BMS) is a chronic pain of a burning quality affecting the tongue and intraoral mucosa. Currently, there are no definite diagnostic criteria; therefore, the diagnosis is made by exclusion of potential local and systemic causes that could justify the burning sensation. The etiology behind primary BMS remains unclear; however, the most acceptable theories link primary BMS with neuropathic pain. This article provides a review of primary BMS diagnosis, mechanisms, and treatment with focus on the association of BMS with pain modulation. Preliminary data are presented suggesting a link between primary BMS and a faulty inhibitory pain system.

What should we tell patients with painful temporomandibular disorders about what to eat?

BACKGROUND AND OVERVIEW: Patients with painful temporomandibular disorders (TMD) commonly report problems eating, owing to limited mandibular opening and pain and discomfort with biting and chewing. Consequently, painful TMD may affect dietary intake and nutritional status. CONCLUSIONS: Treatment of painful TMD is multifaceted and involves pharmacologic, physical, and cognitive behavior and dietary therapies. Painful TMD may influence the quality of dietary intake and eating behaviors. There is a dearth of established guidelines and validated measures that clinicians can use to assess and manage diet and nutritional well-being in patients with this disorder. The authors present recommendations in an effort to guide clinicians on how to help patients with painful TMD improve the quality of their diets and avoid or minimize eating-related pain. PRACTICAL IMPLICATIONS: Providing comprehensive care for patients with painful TMD should include diet evaluation and recommendations for eating comfortably and supporting nutrition. An interprofessional approach may help improve treatment outcomes. Research is needed to develop evidence-based guidelines for diet and nutrition that clinicians can use in the care of patients with painful TMD.