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.

Trigeminal neuropathy presenting secondary to SARS-CoV-2 infection.

Introduction: A 58-year-old woman presented to a multidisciplinary facial pain clinic in October 2021 complaining of a constant pain in the right side of her face since contracting coronavirus SARS-CoV-2 18 months earlier. The pain extending from the right temple down to her right cheek extraorally and including the maxillary teeth and right side of tongue intraorally. This was accompanied by anosmia, diplopia on lateral gaze, and dizziness. Methods: Clinical examination was supplemented with several neurophysiological tests to confirm the diagnosis including an MRI brain scan, quantitative sensory testing, electrophysiological blink reflex testing, corneal confocal microscopy, and pain and short-form anxiety and depression questionnaires. Results: Quantitative sensory testing showed unilateral loss of perception in thermal and mechanical sensibility and bilateral hyperalgesia indicating central sensitization. Bilateral corneal confocal microscopy showed an abnormally reduced corneal nerve fibre length on the right side. MRI, blink reflex, and masseter inhibitory testing findings were normal. Conclusion: This case study is the first case of trigeminal neuropathy related to SARS-CoV-2 infection reported in the literature. It also discusses the successful management of the patient's trigeminal neuropathic pain.

Electrical stimulation to clinically identify position of the lingual nerve: results of 50 subjects with reliability and correlation with MRI.

PURPOSE: Recently we described mapping of the lingual nerve clinically in patients using electrical nerve stimulation. This paper reports results of a larger study with inter- and intra-observer reliability and comparison with positional measurements from magnetic resonance imaging (MRI). METHODS: In 50 healthy participants, measurements were taken when subjects felt a tingling sensation in the tongue induced by a stimulation probe over the lingual nerve. Three positions were measured in relation to the third molar. Measurement reliability was tested for both inter-observer and intra-observer agreement and positional data of the lingual nerve measured clinically was also compared with nerve position as measured from MRI scans. RESULTS: Out of 50 participants, 96 nerves (49 = left/47 = right) were included in the study. The lingual nerve was identified in 90% (87) of this sample. The mean of height of the nerve in points A, B and C were 9.64 mm, 10.77 mm and 12.34 respectively. Inter-and intra-observer agreement was considered to be good to excellent (ICC = 0.8-0.96). Agreement between nerve mapping measured values and MRI measured values was good (ICC < 0.6). CONCLUSION: This technique may prove useful for the clinical determination of lingual nerve position prior to procedures in the third molar region.

Orofacial pain in 1916 patients with early or moderate Parkinson disease.

INTRODUCTION: Several studies have reported that some types of orofacial pain are more common in patients with Parkinson disease (PD) than the general population. OBJECTIVES: In this study, we aimed to investigate the prevalence of self-reported orofacial pain in a larger group of patients with PD than has been previously studied. METHODS: We analysed data from 1916 participants with PD in a cross-sectional study recruited to the UK Parkinson's Pain Study who had detailed assessments of pain, motor, and nonmotor symptoms. The King's Parkinson's Pain scale was used to quantify different subtypes of pain. RESULTS: A total of 139 (7.3%) patients reported the presence of some form of orofacial pain. Burning mouth syndrome was reported in 32 (1.7%), whereas chewing pain was found in 38 (2.0%) and grinding pain in 78 (4.0%). Orofacial pain was significantly more common in females (10.4%) than males (5.9%). Multiple logistic regression analysis showed a significant association between orofacial pain and pain severity, neuropathic pain, and oral motor and nonmotor dysfunction. CONCLUSION: In our study, population cohort of early patients with PD found prevalence of orofacial pain conditions similar to that in the general population.

Corneal Confocal Microscopy Detects Small-Fiber Neuropathy in Burning Mouth Syndrome: A Cross-Sectional Study.

AIMS: To assess the utility of corneal confocal microscopy in identifying small fiber damage in patients with burning mouth syndrome (BMS). METHODS: A prospective cross-sectional cohort study was conducted at two United Kingdom dental hospitals between 2014 and 2017. A total of 17 consecutive patients with idiopathic BMS aged between 18 and 85 years and 14 healthy age-matched control subjects were enrolled in this study. Corneal subbasal nerve plexus measures were quantified in images acquired using a laser-scanning in vivo corneal confocal microscope. The main outcome measures were corneal nerve fiber density, nerve branch density, nerve fiber length, and Langerhans cell density. RESULTS: Of the 17 patients with BMS, 15 (88%) were women, and the mean (standard deviation) age of the sample was 61.7 (6.5) years. Of the healthy controls, 7 (50%) were women, and the mean (standard deviation) age was 59.3 (8.68) years. Corneal nerve fiber density (no./mm2) (BMS: 29.27 ± 6.22 vs controls: 36.19 ± 5.9; median difference = 6.71; 95% CI: 1.56 to 11.56; P = .007) and corneal nerve fiber length (mm/mm2) (BMS: 21.06 ± 4.77 vs controls: 25.39 ± 3.91; median difference = 4.5; 95% CI: 1.22 to 6.81; P = .007) were significantly lower in BMS patients compared to controls, and Langerhans cell density (no./mm2) (BMS: 74.04 ± 83.37 vs controls: 29.17 ± 45.14; median difference = -21.27; 95% CI: -65.35 to -2.91; P = .02) was significantly higher. CONCLUSION: Using a rapid noninvasive ophthalmic imaging technique, this study provides further evidence for small fiber damage in BMS and has potential utility for monitoring disease progression and/or response. Furthermore, this technique shows a hitherto undocumented increased density of immune cells in this group of patients.

Formulation and optimisation of novel transfersomes for sustained release of local anaesthetic.

OBJECTIVE: To investigate the effect of formulation parameters on the preparation of transfersomes as sustained-release delivery systems for lidocaine and to develop and validate a new high-performance liquid chromatography (HPLC) method for analysis. METHOD: Taguchi design of experiment (DOE) was used to optimise lidocaine-loaded transfersomes in terms of phospholipid, edge activator (EA) and phospholipid : EA ratio. Transfersomes were characterised for size, polydispersity index (PDI), charge and entrapment efficiency (%EE). A HPLC method for lidocaine quantification was optimised and validated using a mobile phase of 30%v/v PBS (0.01 m) : 70%v/v Acetonitrile at a flow rate of 1 ml/min, detected at 255 nm with retention time of 2.84 min. The release of lidocaine from selected samples was assessed in vitro. KEY FINDINGS: Transfersomes were 200 nm in size, with PDI ~ 0.3. HPLC method was valid for linearity (0.1-2 mg/ml, R2 0.9999), accuracy, intermediate precision and repeatability according to ICH guidelines. The %EE was between 44% and 56% and dependent on the formulation parameters. Taguchi DOE showed the effect of factors was in the rank order : lipid : EA ratio Ëƒ EA type Ëƒ lipid type. Optimised transfersomes sustained the release of lidocaine over 24 h. CONCLUSION: Sustained-release, lidocaine-loaded transfersomes were successfully formulated and optimised using a DOE approach, and a new HPLC method for lidocaine analysis was developed and validated.

Surfactant Effects on Lipid-Based Vesicles Properties.

Understanding the effect of surfactant properties is critical when designing vesicular delivery systems. This review evaluates previous studies to explain the influence of surfactant properties on the behavior of lipid vesicular systems, specifically their size, charge, stability, entrapment efficiency, pharmacokinetics, and pharmacodynamics. Generally, the size of vesicles decreases by increasing the surfactant concentration, carbon chain length, the hydrophilicity of the surfactant head group, and the hydrophilic-lipophilic balance. Increasing surfactant concentration can also lead to an increase in charge, which in turn reduces vesicle aggregation and enhances the stability of the system. The vesicles' entrapment efficiency not only depends on the surfactant properties but also on the encapsulated drug. For example, the encapsulation of a lipophilic drug could be enhanced by using a surfactant with a low hydrophilic-lipophilic balance value. Moreover, the membrane permeability of vesicles depends on the surfactant's carbon chain length and transition temperature. In addition, surfactants have a clear influence on pharmacokinetics and pharmacodynamics such as sustaining drug release, enhancing the circulation time of vesicles, improving targeting and cellular uptake.

Structural and functional changes in HDL with low grade and chronic inflammation.

OBJECTIVE: HDL functionality has been shown to be impaired in inflammatory conditions, including coronary artery disease. The present study aims to determine the impact of low grade and acute inflammation on HDL function and structure. APPROACH AND RESULTS: i) The endothelial protective effects of HDL were compared between 26 periodontal patients and 26 age and sex matched controls by measuring paraoxonase activity in serum and nitric oxide bioavailability and superoxide production in endothelial cells. Paraoxonase activity and nitric oxide bioavailability were reduced, while superoxide production was increased (p<0.01) in periodontal patients compared to controls. ii) HDL function, including cholesterol efflux and vascular cell adhesion molecule-1 expression, was subsequently measured in the periodontal patients following an inflammatory stimulus. There was an acute deterioration in HDL's endothelial protective function, without change in cholesterol efflux, after 24h (p<0.01 for all). These functional changes tracked increases of inflammatory markers and altered HDL composition. Finally, HDL function returned to baseline levels after resolution of inflammation. CONCLUSION: This study demonstrates that even minor alterations in systemic inflammation can impair the endothelial protective effects of HDL. These functional changes were independent of cholesterol efflux and were associated with remodeling of the HDL proteome. All measures of HDL's endothelial protective functions recovered with resolution of inflammation. These findings suggest that HDL dysfunction may represent a novel mechanism linking inflammation with progression of atheroma.

Reproducibility and biological variability of HDL's vascular functional assays.

BACKGROUND: Recent failures of clinical trials promoting HDL-elevating therapies have prompted research groups to focus on its functional activity in disease. Endothelial effects of HDL can be measured with in vitro cell assays. The reproducibility and biological relevance of these assays have not been explored both in healthy individuals and those at increased cardiovascular (CV) risk. METHODS: HDL dependent nitric oxide (NO) bioavailability, superoxide (SO) production and serum paraoxonase-1 (PON-1) activity were measured in 35 healthy adults (34.37 24-49) and 8 patients (43.56 37-49) suffering from a chronic inflammatory condition (periodontitis-PD). Assay reproducibility was assessed by independent technicians on consecutive days to determine inter and intra analyser variability for each assay. The 35 healthy individuals were further divided into young (n = 16) and middle aged (n = 19) groups and compared with regards to HDL functions. Within-subject biological variation of HDL function was determined in a sub-group of 25 healthy volunteers at intervals of one day and 1 month, and in 8 patients at intervals of one day and 1 week. Power curves were also generated to estimate the number of patients that would be required for HDL functional assays in a cross-over and parallel study design. RESULTS: NO bioavailability was the most reproducible assay in healthy adults (coefficient of variation = 1.72%, 1.92 - intra and inter respectively) and PD patients (CV = 4.4% and 5.5%). All measures demonstrated no statistical difference between young and healthy middle aged population. No single assay demonstrated significant variations over time, indicating that within patient variations are negligible. Our power curves for NO bioavailability and PON-1 activity suggest that low number of patients will be required to detect significant differences in HDL function in a cross over and parallel study design. CONCLUSION: This study suggests that in vitro HDL functional assays are reliable and can be used to assess HDL functionality in healthy and diseased populations. NO bioavailability was the most reproducible assay, but PON-1 activity remains the most practical for application in clinical trials due to its capacity for scale.