Photobiomodulation alleviates Burning Mouth Syndrome pain: Immediate and weekly outcomes explored.

Burning Mouth Syndrome (BMS) is an intraoral chronic burning or dysesthetic sensation, without clinically evident causative lesions on clinical examination and investigation. AIM: To assess immediate and weekly effects of photobiomodulation (PBM) on BMS patients. METHODS: Thirty BMS patients were treated intra-orally with photobiomodulation 940(±10) nm (InGaAsP) 3 W, semi-conductor diode, weekly, for up to 10 weeks. Pain intensity, measured using the Visual Analogue Scale (VAS), and characteristics were recorded immidiately after each treatment, along with a weekly average VAS. RESULTS: Immediate mean VAS score decreased from a starting score of 7.80 ± 1.83 to 2.07 ± 2.55 (p < 0.001). The mean weekly VAS score for the week after the final treatment session was higher (5.73 ± 2.80, p < 0.001) than the immediate response, but still significantly lower than the starting score (p = 0.017). We observed a trend of pain improvement with more treatments, but this was only statistically significant up to the third treatment. Male gender and unilateral pain correlated with better PBM efficacy (p = 0.017, 0.022, respectively). CONCLUSION: PBM provides significant immediate pain relief for BMS patients after each treatment; however, the efficacy decreases notably over the following week. A trend of increasing pain relief across treatments was observed, statistically significant up to the third treatment.

Quantitive Assessment of Gustatory Function and Its Association with Demographics, and Systemic Morbidity.

This study aimed to analyze the associations of gustatory dysfunction as measured by validated taste strips with demographics and co-morbidities. This cross-sectional study retrospectively analyzed records of patients who attended the Orofacial Chemosensory Center of Hadassah Medical Center between 2017 and 2020. Taste strips were used as a validated method to determine taste dysfunction. A total of 272 subjects were included, 137 (50.4%) women and 135 (49.6%) men, with a mean age of 53.5 ± 19.3 years and age range of 18-98 years. The total taste score among the study population was 8.53 ± 4.03 (scale range 0-16). Age had a significant negative correlation with the total taste score (p = 0.001), and men exhibited worse total (p < 0.001), salty (p = 0.003), and bitter (p < 0.001) scores. Major trauma was associated with worse total (p < 0.001) and specialized taste assessments (sweet (p = 0.001), sour (p = 0.002), salty (p = 0.016), and bitter (p < 0.001)). Chemotherapy was associated with reduced total (p < 0.001), salty (p = 0.003), and bitter (p = 0.001) taste scores. Zinc deficiency exhibited worse salty (p = 0.027) and total (p = 0.038) taste scores. Patients with burning mouth syndrome (BMS) showed higher salty scores (p = 0.017). Patients who experienced exposure to toxic chemicals exhibited worse salty scores (p = 0.024). We conclude that gustatory dysfunction is associated with older age, male sex, and co-morbidities of major trauma, current chemotherapy, zinc deficiency, BMS, and exposure to toxins. The study highlights the importance of systemic evaluation and quantitive gustatory dysfunction assessment as part of the diagnostic process of patients with subjective complaints of taste disorders.

The anatomical pattern of ductal arborization in parotid glands using cone-beam computerized sialography.

Cone-Beam Computed Tomography-Sialography (Sialo-CBCT) is used to demonstrate salivary ductal structure. This study aimed to conduct a volumetric analysis of the anatomical morphology of Normal-Appearing Glands (NAGs) in parotid sialo-CBCT. Our retrospective study included 14 parotid sialo-CBCT scans interpreted as NAGs in 11 patients with salivary gland impairment. The main duct length and width, as well as number and width of secondary and tertiary ducts were manually evaluated. We found that the main parotid duct showed an average width of 1.39 mm, 1.15 mm, and 0.98 mm, for the proximal, middle and distal thirds, respectively. The arborization pattern showed approximately 20% more tertiary (average number 11.1 ± 2.7) than secondary ducts (average number 9.0 ± 2.4) and approximately 8% narrower tertiary ducts (average width 0.65 ± 0.11 mm) compared to the secondary ducts (average width 0.77 ± 0.14 mm). Our anatomical analysis of NAGs in parotid sialo-CBCT demonstrated progressive narrowing of the main duct and increasing arborization and decreasing lumen size starting from the primary to the tertiary ducts. This is the most updated study regarding the anatomy of the parotid glands as demonstrated in sialo-CBCT. Our results may provide clinicians with the basic information for understanding aberration from normal morphology, as seen in salivary gland pathologies as well facilitate planning of treatment strategies, such as minimally invasive sialo-endoscopies, commonly practiced today.

Patient profiles and success rates under different sedation techniques in a tertiary care center.

OBJECTIVES: Sedation is commonly utilized for individuals otherwise unable to receive dental treatment, such as those with disabilities, medically complex conditions, and dentophobics. The aim was to characterize the profiles of patients receiving various types of sedation and assess the corresponding success rates. METHOD AND MATERIALS: This was a 5-year records-based retrospective study. Data regarding the indication for sedation, medical history, sedation type, and treatments performed were recorded. RESULTS: In total, 103 patients underwent 389 treatment sessions under sedation; 42.7% of the patients were disabled. The most commonly administered sedation was moderate sedation, (49.4%), followed by deep (36.8%) and inhaled sedation (13.9%). Successful treatment results were achieved in 96.1% of sessions, with no adverse effects noted during recovery. The high success rates were independent of patient age, sex, and sedation type. There was a positive association between the indication for sedation and the type of sedation. The medically complex patients and the dentophobic patients received mainly moderate sedation (85.3% and 58.2%, respectively), whereas the disabled patients received deep sedation (51.2%). In total, 94% of patients were returning (re-visiting) patients. A statistically significant association was found between the type of sedation administered and the success rate during the first and last sessions (P < .001). The success rate at the first session may be predictive of the success in subsequent sessions. CONCLUSION: A significant positive correlation was found between patient characteristics and the chosen sedation type leading to a high success rate across the various sedation modalities.

Oxidative stress-mediated proapoptosis signaling: A novel theory on the mechanism underlying the pathogenesis of burning mouth syndrome.

BACKGROUND: Burning mouth syndrome (BMS) is a chronic oral pain disorder characterized by a generalized burning sensation in the oral mucosa without apparent medical or dental causes. Despite various hypotheses proposed to explain BMS pathogenesis, a clear understanding of the cellular-level events and associated histologic and molecular findings is lacking. Advancing our understanding of BMS pathogenesis could facilitate the development of more targeted therapeutic interventions. TYPES OF STUDIES REVIEWED: The authors conducted an extensive literature search and review of cellular mechanisms, focusing on evidence-based data that support a comprehensive hypothesis for BMS pathogenesis. The authors explored novel and detailed mechanisms that may account for the characteristic features of BMS. RESULTS: The authors proposed that BMS symptoms arise from the uncontrolled activation of proapoptotic transmembrane calcium permeable channels expressed in intraoral mucosal nerve fibers. Elevated levels of reactive oxygen species or dysfunctional antiapoptosis pathways may lead to uncontrolled oxidative stress-mediated apoptosis signaling, resulting in upregulation of transmembrane transient receptor potential vanilloid type 1 and P2X 3 calcium channels in nociceptive fibers. Activation of these channels can cause nerve terminal depolarization, leading to generation of action potentials that are centrally interpreted as pain. CONCLUSIONS AND PRACTICAL IMPLICATIONS: The authors present a novel hypothesis for BMS pathogenesis, highlighting the role of proapoptotic transmembrane calcium permeable channels and oxidative stress-mediated apoptosis signaling in the development of BMS symptoms. Understanding these underlying mechanisms could provide new insights into the development of targeted therapeutic interventions for BMS. Additional research is warranted to validate this hypothesis and explore potential avenues for effective management of BMS.

Exploring the Effect of Ethnicity on Chronic Orofacial Pain: A Comparative Study of Jewish and Arab Israeli Patients.

The relationship between ethnicity and chronic pain has been studied worldwide. The population of Israel includes two main ethnic groups, 75% Jews and 21% Arabs. The purpose of this study was to compare orofacial chronic pain characteristics and treatment outcomes between Jewish and Arab Israeli citizens. Two hundred patients admitted to the Orofacial Pain Clinic at Hebrew University-Hadassah School of Dental Medicine between 2017 and 2022 were selected randomly for this historical cohort study. Our cohort included 159 (79.5%) Jews and 41 (20.5%) Arabs. Twenty-six pain-related variables were compared of which only two differed significantly between the two groups, awakening due to pain and mean muscle sensitivity; both indicators were higher in the Arab group (p < 0.05). No differences were found in any of the other variables such as diagnosis, pain severity, onset, and treatment outcome. This minimal difference may be explained by the equal accessibility to medical services for all citizens, and the diversity of our staff that includes Jew as well as Arab service providers. These factors minimize or even eliminate racial bias, language, and cultural barriers, and is reflected in the minor differences in orofacial pain characteristics found between the two main ethnic groups in Israel.

Microbiota-dependent and -independent postnatal development of salivary immunity.

While saliva regulates the interplay between the microbiota and the oral immune system, the mechanisms establishing postnatal salivary immunity are ill-defined. Here, we show that high levels of neutrophils and neonatal Fc receptor (FcRn)-transferred maternal IgG are temporarily present in the neonatal murine salivary glands in a microbiota-independent manner. During weaning, neutrophils, FcRn, and IgG decrease in the salivary glands, while the polymeric immunoglobulin receptor (pIgR) is upregulated in a growth arrest-specific 6 (GAS6)-dependent manner independent of the microbiota. Production of salivary IgA begins following weaning and relies on CD4-help, IL-17, and the microbiota. The weaning phase is characterized by a transient accumulation of dendritic cells capable of migrating from the oral mucosa to the salivary glands upon exposure to microbial challenges and activating T cells. This study reveals the postnatal mechanisms developed in the salivary glands to induce immunity and proposes the salivary glands as an immune inductive site.

Integrated therapy of intraductal irrigations and sialoendoscopies of salivary glands to improve mouth dryness.

OBJECTIVE: To assess the combination of salivary gland intraductal irrigations (IG) followed by sialoendoscopy irrigations (SI) of the parotid gland on the improvement of salivary gland secretory dysfunction (SGSD). METHODS: We retrospectively analyzed the records of SGSD patients who underwent major salivary gland IG followed by SI during 2014-2020. Records included demographics, systemic background, signs, and symptoms. Improvement was assessed by comparing the mean unstimulated and stimulated whole salivary flow rate (UWSF, SWSF) from the baseline point (before IG procedure) to the last point (after SI) using repeated measures. The between-subjects effects of various factors and covariants were analyzed using repeated measures ANCOVA. RESULTS: One hundred patients were included with an age range of 15-83 years (mean age of 60.1 ± 13.1 years). Improvement was detected on UWSF measurements (p = 0.031, F = 3.83), but not on SWSF measurements (p = 0.165, F = 1.85). The between-subjects effects on UWSF measurements were statistically significant for sex (p = 0.003, F = 9.526) and salivary gland manipulators use (p < 0.001, F = 15.107) and for the interaction between sex and salivary gland manipulators use (p- = 0.002, F = 9.709). Results of long-term follow-up for 10.87 ± 11.79 months after the SI procedure demonstrated sustained improvement in UWSF measurements (p = 0.011, F = 4.91). CONCLUSIONS: The combination of IG followed by SI increases UWSF salivary secretion in SGSD patients for a relatively extended duration.

Radiographic findings of space-occupying lesions in sialo-CBCT of the major salivary glands.

OBJECTIVES: When performing CBCT sialography (sialo-CBCT), space-occupying lesions may be identified incidentally. The objective was to describe their radiologic-clinical-histopathologic correlations. METHOD AND MATERIALS: The archive of sialo-CBCT scans was retrospectively searched for suspected space-occupying lesions. Based on the scan and clinical-histopathologic data, the cases were divided into "pathologic" vs "normal," "intra-parenchymal" vs "extra-parenchymal," and "benign" vs "malignant." Two precalibrated, blinded radiologists performed a survey of the radiographic features of each scan. Cohen kappa, chi-square, Kruskal-Wallis, and Mann-Whitney tests assessed inter-observer agreement and radiologic-clinical-histopathologic correlations. RESULTS: In total, 27 (1.5%) suspected space-occupying lesions were found in 1,758 reports. Full follow-up data were available for 15 cases: four were "malignant," six were "benign," and the remaining five were "normal." Kappa showed substantial inter-observer agreement (0.8 to 1.0). Constant swelling correlated with "pathologic" cases (P = .003). Lesion diameter was greater in "pathologic" than "normal" (P < .001) cases, with a cut-off of 12.6 mm. Clinical and radiographic features were similar in "benign" and "malignant" lesions. "Intra-parenchymal" and "extra-parenchymal" space-occupying lesions correlated with "no-fill-region" (P = .01) and "main-duct-displacement" (P = .002), respectively. CONCLUSIONS: Suspected space-occupying lesions in sialo-CBCT with a diameter greater than 12.6 mm are likely to be "pathologic." No radiographic features were able to differentiate between "malignant" and "benign" space-occupying lesions.

Salivary Endocannabinoid Profiles in Chronic Orofacial Pain and Headache Disorders: An Observational Study Using a Novel Tool for Diagnosis and Management.

The endocannabinoid system is involved in physiological and pathological processes, including pain generation, modulation, and sensation. Its role in certain types of chronic orofacial pain (OFP) has not been thoroughly examined. By exploring the profiles of specific salivary endocannabinoids (eCBs) in individuals with different types of OFP, we evaluated their use as biomarkers and the influence of clinical parameters and pain characteristics on eCB levels. The salivary levels of anandamide (AEA), 2-arachidonoyl glycerol (2-AG), and their endogenous breakdown product arachidonic acid (AA), as well as the eCB-like molecules N-palmitoylethanolamide (PEA) and N-oleoylethanolamide (OEA), were assessed in 83 OFP patients and 43 pain-free controls using liquid chromatography/tandem mass spectrometry. Patients were grouped by diagnosis: post-traumatic neuropathy (PTN), trigeminal neuralgia (TN), temporomandibular disorder (TMD), migraine, tension-type headache (TTH), and burning mouth syndrome (BMS). Correlation analyses between a specific diagnosis, pain characteristics, and eCB levels were conducted. Significantly lower levels of 2-AG were found in the TN and TTH groups, while significantly lower PEA levels were found in the migraine group. BMS was the only group with elevated eCBs (AEA) versus the control. Significant correlations were found between levels of specific eCBs and gender, health-related quality of life (HRQoL), BMI, pain duration, and sleep awakenings. In conclusion, salivary samples exhibited signature eCBs profiles for major OFP disorders, especially migraine, TTH, TN, and BMS. This finding may pave the way for using salivary eCBs biomarkers for more accurate diagnoses and management of chronic OFP patients.

Topical tretinoin treatment for burning mouth syndrome: a pilot study.

OBJECTIVES: Burning mouth syndrome is an intraoral chronic pain condition characterized by a moderate to severe sensation of burning from the oral mucosa. No clinical signs are found and there is no efficient treatment. METHOD AND MATERIALS: This pilot study included 10 women that were resistant to other previous treatments or noncompliant to systemic medications. Patients were asked to apply tretinoin gel 0.05% on their tongues twice daily for 14 days. Treatment effectiveness was assessed by completing a pre-study psychologic questionnaire and recording a daily wellbeing and pain log. RESULTS: Significant pain-score decrease in 50% of the patients (delta numerical rating score -3.15 ± 3.02, P value = .005) was recorded. This finding was in concordance with the verbal statements including major quality-of-life improvement (P value = .05), without any treatment positive or negative predictive factors. CONCLUSIONS: Topical tretinoin exhibits potential efficacy in patients with treatment resistant burning mouth syndrome and may also be used as a primary treatment modality.

Reduced Endocannabinoid Tone in Saliva of Chronic Orofacial Pain Patients.

BACKGROUND: the endocannabinoid system (ECS) participates in many physiological and pathological processes including pain generation, modulation, and sensation. Its involvement in chronic orofacial pain (OFP) in general, and the reflection of its involvement in OFP in salivary endocannabinoid (eCBs) levels in particular, has not been examined. OBJECTIVES: to evaluate the association between salivary (eCBs) levels and chronic OFP. METHODS: salivary levels of 2 eCBs, anandamide (AEA), 2-arachidonoylglycerol (2-AG), 2 endocannabinoid-like compoundsN-palmitoylethanolamine (PEA), N-oleoylethanolamine (OEA), and their endogenous precursor and breakdown product, arachidonic acid (AA), were analyzed using liquid chromatography/tandem mass spectrometry in 83 chronic OFP patients and 43 pain-free controls. The chronic OFP patients were divided according to diagnosis into musculoskeletal, neurovascular/migraine, and neuropathic pain types. RESULTS: chronic OFP patients had lower levels of OEA (p = 0.02) and 2-AG (p = 0.01). Analyzing specific pain types revealed lower levels of AEA and OEA in the neurovascular group (p = 0.04, 0.02, respectively), and 2-AG in the neuropathic group compared to controls (p = 0.05). No significant differences were found between the musculoskeletal pain group and controls. Higher pain intensity was accompanied by lower levels of AA (p = 0.028), in neuropathic group. CONCLUSIONS: lower levels of eCBs were found in the saliva of chronic OFP patients compared to controls, specifically those with neurovascular/migraine, and neuropathic pain. The detection of changes in salivary endocannabinoids levels related to OFP adds a new dimension to our understanding of OFP mechanisms, and may have diagnostic as well as therapeutic implications for pain.

The Impact of Expectation for Pain Relief on Orofacial Pain Treatment Outcomes.

Aims: To examine the effects of expectations for pain relief on the objective and subjective outcome of chronic orofacial pain (OFP) treatment. Materials and Methods: Sixty individuals referred to the Orofacial Pain Clinic at the Hebrew University-Hadassah School of Dental Medicine between 2015 and 2017 with OFP reported their expectation for pain relief upon initial consultation. They were also interviewed by telephone after treatment and asked to recall their expectations, referred to as "recalled expectations" (RE). Correlations between RE and treatment success were calculated from pain diaries, and from subjective pain improvement rates (PIR) reported by the patients. Results: 21 males (35.0%) and 39 females (65%), mean age of 46.90 ± 15.77 years and mean pain duration of 49.07 ± 51.95 months participated in the study. All participants rated their expectations as "10" on a 0 to 10 scale during their first visit. RE did not correlate with diary ratings, (P = 0.773) but inversely correlated (-0.3) with PIR (P = 0.020) treatment outcomes. Conclusions: Expectations for pain relief, reported as 10 on a 0-10 scale during the first appointment, may reflect the patient's desire for complete relief of their pain rather than their expectations. Clinicians should therefore be aware of the need for clear communication and wording when examining for expectations. Inverse correlation between recalled expectations and subjective outcome may be due to the nature of recalled expectations when patients already knew their treatment outcomes, and may be explained by the concept of cognitive dissonance.

Standardization of terminology, imaging features, and interpretation of CBCT sialography of major salivary glands: a clinical review.

Sialography combined with cone beam computerized tomography (sialo-CBCT) is an imaging technique that demonstrates the ductal system of the major salivary glands and allows evaluation of gland function. This review describes the sialo-CBCT technique, terminology, common pitfalls and limitations, as well as radiographic features and suggested pathogenicity of various salivary gland disorders, based on 1,758 sialo-CBCT examinations conducted over the last decade in one institution, and the current literature. The adoption of standardized terminology is proposed to prevent miscommunication, facilitate formulation of differential diagnoses, and thereby promote patient management: (1) Sialo-CBCT requires specific training, and operator experience is required for adequate glandular filling with minimal extravasation; (2) Limit injection-to-scan time to avoid pre-mature emptying; (3) The sialo-CBCT report should include a description of the morphology of the primary duct as well as the secondary, tertiary, and descending branches, the maximal branching level, the presence of sialectasis, overall glandular size, and parenchymal findings; (4) Functional evaluation is based on assessment of iodine clearance in the post evacuation image; (5) Sialectasis and ductopenia are the main findings in Sjogren syndrome and recurrent juvenile parotitis; (6) Sialodochitis with or without fillings defects or hyperdense calcifications characterize obstructive sialadenitis and sialolithiasis; (7) The findings following radioactive-iodine-induced damage are similar to obstructive sialadenitis, with atrophy in late stages; (8) In chronic graft-versus-host disease (cGVHD), variable presentations of ductopenia, sialectasis, and sialodochitis may be evident; (9) The red flags indicating a space-occupying lesion include areas of no filling, splaying of ducts, and primary duct deviation.

Serological and hematological characteristics of Sjogren's syndrome and dry eye syndrome patients using a novel immune serology technique.

OBJECTIVES: To compare hematologic and serological parameters among patients with Sjogren's syndrome (SS), dry eye syndrome (DES) and controls, and validate a novel multiplex-serology method for identifying auto-antibodies in these populations. METHODS: In a clinic-based case-control study a total of 422 participants were recruited, including 91 with SS, 120 DES, and 211 controls (age and sex frequency-matched). We measured blood counts, anti-nuclear-antibodies (ANA), anti-SSA/SSB, anti-ribonucleoprotein (RNP), anti-double-stranded-DNA (DS-DNA), and rheumatoid factor (RF) using the "Immunodot" qualitative-ELISA assay. Immunoglobulins, C3 and C4 were measured by immune-fluorescence. Autoantibodies were also quantified with a newly-developed method using glutathione-S-transferase fusion proteins of SSA/Ro 52 and 60kD and SSB/La (multiplex-serology), measuring median fluorescence intensity (MFI). RESULTS: Among DES patients, only 2% (95%CI: 0.36-6.3) had positive immune serology. SS patients had lower lymphocyte, hemoglobin and C3 levels but higher prevalence of RF, ANA, anti-SSA/B and higher IgG and MFI levels, compared to DES and controls (P<0.001). Presence of anti-SSA/Ro-52kD was associated with SS [odds ratio (OR) = 2.05, 95% confidence interval (CI): 1.46-2.88]. Anti-SSB/La was inversely associated with DES (OR = 0.81, 95%CI: 0.65-1.00) compared to controls. Positivity to RF (adjusted for age, gender and ethnicity OR = 5.03, 95%CI: 1.78-14.21), ANA (OR = 14.75, 95%CI: 4.09-53.17), or combination of anti-SSA/B (OR = 20.97, 95%CI: 4.60-95.54) were more likely in SS compared to DES. The novel multiplex-serology method correctly identified anti-SSA/B autoantibodies by ELISA among SS, DES patients and controls (sensitivity = 1.0, negative-predictive-value = 1.0). CONCLUSIONS: Serologic parameters distinguish SS from DES patients and controls. A newly-developed multiplex-serology technique may be useful to detect autoantibodies in large epidemiologic studies.

Inhalation Sedation During the COVID-19 Outbreak: An Expert Opinion.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the pathogen that causes coronavirus disease-2019 (COVID-19), is thought to be transmitted via droplets and aerosols, and was detected in saliva of infected individuals. These droplets from the upper airway may infect the inhalation sedation mask and tubing. The authors determined the adequate measures needed to prevent the transmission of COVID-19 by nitrous-oxide (N2O) system during inhalation sedation in dentistry and provided evidence on mask and tubing sterilization. Additional measures to protect patients and healthcare workers from COVID-19 that may be transmitted by the inhalation sedation system are discussed. The authors recommend minimal use of a N2O system during inhalation sedation in dentistry. In case of need, the practitioners should have more than one scavenger kit and nasal masks for each N2O/O2 mixer. Biologic barriers should be mounted between the scavenger's tubing and the central evacuation system. Strict cleansing and sterilization should be performed for all parts of the N2O system. The use a disposable scavenger system and nasal mask should be considered as a viable option.

Minor salivary glands: Clinical, histological and immunohistochemical features of common and less common pathologies.

Hundreds of minor salivary glands (MiSGs) are scattered in the oral cavity located at the submucosa layer. Beside their role in the oral cavity lubrication and immunity defence system, MiSGs are beneficial tissue source for diagnosing oral and non-oral related diseases. The advantage of MiSGs as a diagnostic tool reside on their fairly simple excisional procedure on one hand and negligible impact of the normal secretion capability of the salivary gland system on the other hand. The review focuses on pathologies related to developmental, reactive, metabolic, inflammatory and immunologic conditions, Iatrogenic causes and other undefined causes.