Evaluation of patients suffered from burning mouth syndrome and persistent idiopathic facial pain using Japanese version PainDETECT questionnaire and depression scales.

BACKGROUND/PURPOSE: Various questionnaires have been validated as methods for screening of neuropathic pain, but none have been established for the orofacial region. Although chronic pain and depression are likely to comorbid, few studies have examined the relationship between orofacial chronic pain and depression. Therefore, we evaluated the potential of the Japanese Version of PainDETECT as an assessment tool for neuropathic pain associated with burning mouth syndrome (BMS) and persistent idiopathic facial pain (PIFP). We also evaluated the depression scale such as Beck's Depression Inventory (BDI: a subjective index) and Hamilton Depression Rating Scale (HDRS: an objective index) with BMS or PIFP. MATERIALS AND METHODS: As a target, we administered the Japanese version of the PainDETECT questionnaire to the BMS (29 patients) and PIFP (17 patients). As a control, patients with post-extraction pain (typical nociceptive pain, (EXT) 16 patients) were also participated. We performed BDI and HDRS with BMS or PIFP. RESULTS: Although PainDETECT final score was significantly higher in BMS [median: 10] compared with PIFP [6] and EXT [5] (p < 0.05), PainDETECT final scores for all groups were lower than the cutoff value for the possibility of neuropathic pain. HDRS was significantly higher in the BMS than the PIFP. There were no significant differences between the BMS and PIFP in BDI. CONCLUSION: Under the limitations of current research design, the Japanese version of the PainDETECT questionnaire does not show sufficient potential as pain assessment tool for patients with BMS and PIFP. BMS is comorbid with depression objectively when compared with PIFP.

Evaluation of Scoring Systems for Airway Management After Oral Cancer Surgery: A Retrospective Study.

OBJECTIVE: Postoperative airway obstruction following oral cancer surgery is difficult to predict. Scoring systems used to assess the need for tracheotomy use risk factors as criteria. We aimed to examine whether these clinical scoring systems can predict airway obstruction following oral cancer surgery. METHODS: We assessed 95 patients who underwent oral cancer surgery without tracheotomy under general anesthesia between January 2007 and April 2019. We reviewed multiple factors from the patients' medical records, including age, sex, tumor site, body mass index, tumor stage, type of surgery, airway management method, Cameron and Gupta scores, and postoperative airway complications. RESULTS: Tumors were located in the maxilla (n = 14), buccal mucosa (n = 13), mandible (n = 14), floor of the mouth (n = 6), and tongue (n = 48). Twenty-seven patients (28.4%) were graded as Stage 1, 37 patients (38.9%) as Stage 2, 9 patients (9.5%) as Stage 3, and 3 (3.2%) patients as Stage 4. Nine patients (9.5%) had local recurrences, and ten patients (10.5%) had neck metastases. Postoperative oxygen administration alone failed to improve dyspnea in 4 patients (4.2%). The median Cameron scores between patients with and without airway trouble were not significantly different (P = 0.226). However, a significant difference was observed in median Gupta scores between patients with and without airway trouble (P = 0.01). We created a receiver operating characteristic curve to predict postoperative airway trouble based on the preoperative Gupta score; the area under the curve was 0.856 (95% confidence interval: 0.61-1). A Gupta score cutoff value of 3.0 had a sensitivity of 92.3% and specificity of 75.0%. CONCLUSIONS: Screening based on the Gupta score appears to be effective in predicting postoperative airway obstruction. We propose that this screening tool can be used to better plan tracheotomy and other airway management strategies during preoperative patient assessment.

Serum Metabolic Profiles of the Tryptophan-Kynurenine Pathway in the high risk subjects of major depressive disorder.

Previous reports have shown that during chronic inflammation, the tryptophan (TRP)-kynurenine (KYN) pathway plays a pivotal role in the onset of depression. The aim of this study was to investigate the characteristics of the serum TRP-KYN pathway metabolite profile in high-risk subjects of major depressive disorder (HRMDD) defined by depression scores. The concentrations of TRP-KYN pathway metabolites {TRP, KYN, 3-hydroxyanthranilic acid (3HAA), 3-hydroxykynurenine (3HK), kynurenic acid (KYNA) and anthranilic acid (AA)} were assessed in serum from HRMDD, chronic pain disorder patients and healthy controls. In serum from HRMDD, elevated levels of AA and decreased levels of TRP were observed, but the levels of other metabolites were not changed. Furthermore, the change in the AA2nd/AA1st ratio in subjects who progressed from a health. y state to a depressive state was correlated with an increase in the CES-D score. The level of IL-1 receptor antagonist (IL-1RA) was negatively correlated with that of AA. Interestingly, we confirmed AA as a possible biomarker for depression-related symptoms, since the metabolite profiles in the chronic pain disorder group and chronic unpredictable mild stress model mice were similar to those in the HRMDD. These results suggest that AA may be an effective marker for HRMDD.

Effect of antidepressant treatment on plasma levels of neuroinflammation-associated molecules in patients with somatic symptom disorder with predominant pain around the orofacial region.

OBJECTIVE: Burning mouth syndrome (BMS) and atypical odontalgia (AO) are examples of somatic symptom disorders with predominant pain around the orofacial region. Neuroinflammation is thought to play a role in the mechanisms, but few studies have been conducted. We aimed to better understand the role of neuroinflammation in the pathophysiology and treatment of BMS/AO. METHODS: Plasma levels of 28 neuroinflammation-related molecules were determined in 44 controls and 48 BMS/AO patients both pretreatment and 12-week post-treatment with duloxetine. RESULTS: Baseline plasma levels of interleukin (IL)-1ß (p < .0001), IL-1 receptor antagonist (p < .001), IL-6 (p < .0001), macrophage inflammatory protein-1ß (p < .0001), and platelet-derived growth factor-bb (.04) were significantly higher in patients than in controls. Plasma levels of granulocyte macrophage colony stimulating factor were significantly higher in patients than in controls (p < .001) and decreased with treatment (.009). Plasma levels of eotaxin, monocyte chemoattractant protein-1, and vascular endothelial growth factor decreased significantly with treatment (p < .001, .022, and .029, respectively). CONCLUSIONS: Inflammatory mechanisms may be involved in the pathophysiology and/or treatment response of somatic symptom disorders with predominant pain around the orofacial region.

Duloxetine Plasma Concentrations and Its Effectiveness in the Treatment of Nonorganic Chronic Pain in the Orofacial Region.

OBJECTIVE: The purpose of this study was to examine the relationship between the pain-relieving effects of duloxetine and its plasma concentrations in patients with burning mouth syndrome and atypical odontalgia characterized by chronic nonorganic pain in the orofacial region. METHODS: We administered duloxetine to 77 patients diagnosed as having burning mouth syndrome or atypical odontalgia for 12 weeks. The initial dose of duloxetine was established as 20 mg/d and was increased to 40 mg/d after week 2. We evaluated pain using the visual analog scale and depressive symptoms using the Structured Interview Guide for the Hamilton Depression Rating Scale at weeks 0, 2, 4, 6, 8, 10, and 12 and measured plasma concentrations of duloxetine 12 weeks after the start of its administration. RESULTS: Visual analog scale scores were significantly lower 12 weeks after than at the start of the administration of duloxetine (paired t test, t = 6.65, P < 0.0001). We examined the relationship between the rate of decreases in visual analog scale scores and plasma concentrations of duloxetine. There was no significant linear regression or quadratic regression. CONCLUSIONS: Duloxetine significantly relieved pain in patients with chronic nonorganic pain in the orofacial region. However, no relationship was observed between its pain-relieving effects and plasma concentrations.

Computed Tomographic Estimation of Particulate Cancellous Bone and Marrow Weight for Successful Transplant in Unilateral Cleft Lip and Palate Patients.

OBJECTIVE: The defect volume measured on computed tomography (CT) for secondary bone graft (SBG) is well correlated to the actual amount of particulate cancellous bone and marrow (PCBM) transplanted in unilateral cleft lip and palate (UCLP) patients. However, the validity of such measurements have not been completely verified due to lack of evaluation of treatment results. The objective of this study was to propose an estimation method by CT based on the data of successfully treated patients. For this purpose, the association was initially verified between the weight of transplanted PCBM and the defect volume measured on CT using the results of successfully treated patients. METHODS: Treatment results were evaluated 1 year after SBG by intraoral radiography in 50 UCLP patients. For the patients with good results, the correlation was investigated between the defect volume on CT and the transplanted PCBM weight, and a method was proposed based on PCBM density, calculated as PCBM weight divided by defect volume on CT. RESULTS: In successfully treated patients showing level 3 or 4 alveolar resorption, a strong correlation (r = .87) was found between the volume on CT and the PCBM weight. Level 4 results were observed in 22 of 23 (95.7%) patients who had calculated PCBM densities of more than 6 g/cm3. CONCLUSIONS: Volume estimation on preoperative CT was confirmed to have sufficient validity. The weight of PCBM transplanted should be greater than the defect volume on CT multiplied by 6.

Five Patients With Burning Mouth Syndrome in Whom an Antidepressant (Serotonin-Noradrenaline Reuptake Inhibitor) Was Not Effective, but Pregabalin Markedly Relieved Pain.

Burning mouth syndrome (BMS) causes idiopathic pain or a burning sensation in clinically normal oral mucosa. Burning mouth syndrome is a chronic disease with an unknown etiology. Burning mouth syndrome is also idiopathic, and a consensus regarding diagnosis/treatment has not been reached yet. Recent studies have supported the suggestion that BMS is a neuropathic pain disorder in which both the peripheral and central nervous systems are involved. Tricyclic antidepressants (nortriptyline and amitriptyline), serotonin-noradrenaline reuptake inhibitors (SNRIs) (duloxetine and milnacipran), and antiepileptic drugs, potential-dependent calcium channel α2δ subunit ligands (gabapentine and pregabalin), are currently recommended as the first-choice drugs for neuropathic pain. In this study, we report 5 patients with BMS in whom there was no response to SNRI (milnacipran or duloxetine), or administration was discontinued because of adverse reactions, but in whom pregabalin therapy markedly reduced or led to the disappearance of pain in a short period. Pregabalin, whose mechanism of action differs from that of SNRIs, may become a treatment option for BMS patients who are not responsive to or are resistant to SNRIs.

Injectable bone tissue engineering using expanded mesenchymal stem cells.

Patients suffering from bone defects are often treated with autologous bone transplants, but this therapy can cause many complications. New approaches are therefore needed to improve treatment for bone defects, and stem cell therapy presents an exciting alternative approach. Although extensive evidence from basic studies using stem cells has been reported, few clinical applications using stem cells for bone tissue engineering have been developed. We investigated whether injectable tissue-engineered bone (TEB) composed of mesenchymal stem cells (MSCs) and platelet-rich plasma was able to regenerate functional bone in alveolar deficiencies. We performed these studies in animals and subsequently carried out large-scale clinical studies in patients with long-term follow-up; these showed good bone formation using minimally invasive MSC transplantation. All patients exhibited significantly improved bone volume with no side effects. Newly formed bone areas at 3 months were significantly increased over the preoperation baseline (p < .001) and reached levels equivalent to that of native bone. No significant bone resorption occurred during long-term follow-up. Injectable TEB restored masticatory function in patients. This novel clinical approach represents an effective therapeutic utilization of bone tissue engineering.

Potential characteristics of stem cells from human exfoliated deciduous teeth compared with bone marrow-derived mesenchymal stem cells for mineralized tissue-forming cell biology.

INTRODUCTION: Tissue engineering and regenerative medicine using stem cell biology has been a promising field for treatment of local and systemic intractable diseases. Recently, stem cells from human exfoliated deciduous teeth (SHED) have been identified as a novel population of stem cells. This study focused on the characterization of SHED as compared with bone marrow-derived mesenchymal stem cells (BMMSCs). METHODS: We investigated potential characteristics of SHED by using DNA microarray, real-time reverse transcriptase polymerase chain reaction, and immunofluorescence analysis. RESULTS: Multiple gene expression profiles indicated that the expression of 2753 genes in SHED had changed by ≥2.0-fold as compared with that in BMMSCs. One of the most significant pathways that accelerated in SHED was that of bone morphogenetic protein (BMP) receptor signaling, which contains several cascades such as PKA, JNK, and ASK1. When the BMP signaling pathway was stimulated by BMP-2, the expression of BMP-2, BMP-4, Runx2, and DSPP was up-regulated significantly in SHED than that in BMMSCs. Furthermore, the BMP-4 protein was expressed much higher in SHED but not in BMMSCs, as confirmed by immunofluorescence. CONCLUSIONS: By using the gene expression profiles, this study indicates that SHED is involved in the BMP signaling pathway and suggests that BMP-4 might play a crucial role in this. These results might be useful for effective cell-based tissue regeneration, including that of bone, pulp, and dentin, by applying the characteristics of SHED.

Viable cryopreserving tissue-engineered cell-biomaterial for cell banking therapy in an effective cryoprotectant.

The application of cell-biomaterial systems in tissue engineering and regenerative medicine is an important challenge in biomedicine, which preserves not only cells, but also tissue-engineered constructs. In this study, the constructs and cryoprotectant parameters were optimized, and it was evaluated whether the characteristics of dental pulp stem cells (DPSCs), which have high proliferation ability as stem cells, were maintained during encapsulation and cryopreservation. The optimal cell-biomaterial gel constructs with the gelation rate of 2% alginate: 100 mM CaCO(3): 200 mM glucono-δ-lactone (GDL)=4:1:1 and suitable cryoprotectants (CPAs) used for cryopreservation were Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% ethylene glycol (EG), 1.0 M sucrose and 0.00075 M polyvinylpyrrolidone (PVP). Optimality was confirmed by cell viability (trypan blue, live/dead analysis), the proliferation of DPSCs, and the microstructure using scanning electron microscopy (SEM) in the constructs, and surface epitope by flow cytometric analysis before and after cryopreservation. There were no visible differences in the structure. In conclusion, this study indicates that the optimal cell-biomaterial gel constructs and the cryoprotectant are promising biomaterials. The defined encapsulation/thawing system offers an excellent option for cell-banking therapy to be developed with ready-to-use viable biomaterials and patient-specific products as drug delivery systems.

Stem cells from human exfoliated deciduous teeth (SHED) enhance wound healing and the possibility of novel cell therapy.

BACKGROUND AIMS: In recent years, stem cells from human exfoliated deciduous teeth (SHED) have received attention as a novel stem cell source with multipotent potential. We examined the effect on wound-healing promotion with unique stem cells from deciduous teeth as a medical waste. METHODS: An excisional wound-splinting mouse model was used and the effect of wound healing among SHED, human mesenchymal stromal cells (hMSCs), human fibroblasts (hFibro) and a control (phosphate-buffered saline; PBS) was evaluated by macroscopy, histology and enzyme-linked immunosorbent assay (ELISA), and the expression of hyaluronan (HA), which is related to wound healing, investigated. RESULTS: SHED and hMSCs accelerated wound healing compared with hFibro and the control. There was a statistically significant difference in wound healing area among hFibro, hMSCs and SHED compared with the control after day 5. At days 7 and 14 after cell transplantation, the histologic observation showed that transplanted PKH26-positive cells were surrounded by human HA binding protein, especially in hMSCs and SHED. HA expression volume values were 1558.41 ± 60.33 (control), 2092.75 ± 42.56 (hFibro), 2342.07 ± 188.10 (hMSCs) and 2314.85 ± 164.91 (SHED) ng/mg, respectively, and significantly higher in hMSCs and SHED compared with hFibro and control at days 7 and 14 (P < 0.05). CONCLUSIONS: Our results show that SHED hMSCs have similar effects of wound-healing promotion as hFibro and controls. This implies that SHED might offer a unique stem cell resource and the possibility of novel cell therapies for wound healing in the future.

FGFR4 polymorphism, TP53 mutation, and their combinations are prognostic factors for oral squamous cell carcinoma.

The genotype of the fibroblast growth factor receptor 4 (FGFR4) gene and TP53 mutation have been reported as prognostic factors for cancers of the head and neck, bladder, breast and colon. To determine whether they are applicable for oral squamous cell carcinoma (OSCC), we investigated these two genes in OSCC samples from 150 patients who had undergone radical surgery and in 100 cancer-free individuals. In OSCC, the FGFR4 Gly388Arg polymorphism and the presence or absence of mutation in TP53 did not show a significant association with the clinicopathological features of the tumors at surgery. However, the FGFR4 Arg388 allele, as well as mutations in TP53, was found to be closely associated with poor prognosis. Moreover, these two parameters synergistically affected the survival of OSCC patients. During 60 months of observation after radical surgery, a majority of patients with homozygous Arg388 FGFR4 plus mutated TP53 died of cancer, whereas >90% patients carrying homozygous Gly388 FGFR4 plus wild-type TP53 survived. Therefore, the FGFR4 Gly388Arg polymorphism and TP53 mutations, as well as their combinations, are excellent predictors of the prognosis for OSCC patients.