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Oral cenesthopathy (OC) is characterized by unusual oral discomfort without corresponding evidence, and it has often been categorized as "delusional disorder, somatic type". Regarding possible causative factors of OC, involvement of neurovascular contact (NVC) of the trigeminal nerve, which transmits not only pain but also thermal, tactile, and pressure sensations, has never been observed yet. This study aimed to investigate the relationship between clinical characteristics of unilateral OC and the presence of trigeminal nerve NVC. This is a retrospective comparative study that involved 48 patients having predominantly unilateral OC who visited the Psychosomatic Dentistry Clinic of Tokyo Medical and Dental University between April 2016 and February 2019. Magnetic resonance imaging was performed to assess NVC presence. The Oral Dysesthesia Rating Scale (Oral DRS) was used to assess the various oral sensations and functional impairments besides psychometric questionnaires. Clinical characteristics were retrospectively obtained from the patients' medical charts. NVC was present in 45.8% (22/48) of the patients. There was no significant difference in sex, age, psychiatric history, oral psychosomatic comorbidity, and psychometric questionnaire scores between patients with and without NVC. However, compared to the patients with NVC, the patients without NVC had significantly higher scores for overall subjective severity of OC symptoms ( p = 0.008). Moreover, patients having predominantly unilateral OC without NVC showed significantly higher scores in symptom severity and functional impairment of the following parameters: movement ( p = 0.030), work ( p = 0.004), and social activities ( p = 0.010). In addition, compared with the patients with NVC, the patients without NVC showed significantly higher averages of the total symptom severity scale (SSS) and functional impairment scale (FIS) scores in the Oral DRS ( p = 0.015 and p = 0.031, respectively). Furthermore, compared with the patients with NVC, the patients without NVC had significantly higher numbers of corresponding symptoms in both the SSS and FIS ( p = 0.041 and p = 0.007, respectively). While NVC may be involved in the indescribable subtle OC symptoms, more complex mechanisms may also exist in OC patients without NVC, which yield varying and more unbearable oral symptoms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Watanabe, Watanabe, Takao, Hong, Liu, Suga, Tu, Sakamoto, Umezaki, Yoshikawa, Takenoshita, Uezato, Motomura, Kurabayashi, Abiko and Toyofuku.)

Background: Despite improvements in surgical techniques, the removal of vestibular schwannoma is related to some complications. Recovery from surgical complications of vestibular schwannoma is often difficult and complications sometimes lead to permanent deficits. However, treatable trigeminal symptoms may be missed in atypical cases., Case Presentation: A 46-year-old woman complained about burning sensation on her tongue and maxilla for four years before her first visit to our clinic. She visited the neurosurgery department in a university hospital because her facial pain and burning sensation of her tongue were suddenly aggravated. She was diagnosed with vestibular schwannoma and tumour resection was performed. However, her oral pain persisted after surgery. Two months before the initial visit to our clinic, the oral pain became more severe than ever before. When the patient visited a psychiatrist due to a panic attack, the psychiatrist diagnosed her as having somatic symptom disorder and depression and referred her to our clinic. Based on the characteristics of the pain, she was diagnosed as burning mouth syndrome and treated for the same. Within 1.5 months, the pain and burning sensation of the tongue and maxilla almost completely remitted with low dose amitriptyline., Conclusions: Our case suggests that there are exceptional cases in which burning mouth syndrome and vestibular schwannoma occur simultaneously. Burning pain after vestibular schwannoma surgery cannot always be considered a complication of surgery., (© 2021. The Author(s).)

Objectives: So far, the strong link between neuroticism, chronic pain, and depression has been well-documented in literatures. Some suggested that they might share etiological factors, thus resulting in overlapping constructs. However, such effect has never been tested in burning mouth syndrome (BMS) patients, a complex phenomenon influenced by both neuropathic and psychopathological factors. We aim to clarify how personality affects individual's pain and pain-related experiences. Methods: Two hundred forty-eight patients with BMS provided demographic information and psychiatric history; completed Ten-Item Personality Inventory, a Visual Analog Scale of pain, and McGill Pain Questionnaire; and provided adequate parameters of depressive state, catastrophizing thinking, and central sensitization. Results: BMS patients with depression history suffered more severe clinical symptoms and scored higher in neuroticism and less in openness and extraversion than did those without psychiatric diagnoses. After age, sex, and duration of pain were controlled, neuroticism in BMS patients with depression correlates with affective dimension of pain. Instead, if psychiatric history is absent, neuroticism correlates with sensory dimension and pain intensity. In both groups, higher neuroticism, unlike other personality facets, contributed to a more severe clinical condition. Conclusion: Of the five traits, neuroticism appears to be the most crucial dimension associated with the pain symptoms and patient's conditions. This study implies that management of pain must extend beyond solely providing pain-relieving medication and must require a holistic and multidisciplinary approach., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tu, Watanabe, Suga, Hong, Takao, Takenoshita, Motomura and Toyofuku.)

Background: An oral burning sensation with unidentified cause in patients with preexisting psychosocial conditions is usually diagnosed as burning mouth syndrome. However, unexpected organic lesions may be detected in rare cases., Case Presentation: A 35-year-old woman had chief complaints of a burning sensation and numbness of the right side of the lip and tongue, as well as a dry sensation of the mouth with a taste disturbance of the right side of the tongue. The symptoms were continuous and did not show any daily fluctuations. The symptoms started without any recognizable triggering factor six months before her first visit to our clinic,. No abnormality was detected in her mouth. MRI images revealed an approximately 30 × 30 mm well-defined mass localized in the right cerebropontine angle compressing the trigeminal nerve, which was diagnosed as schwannoma of the right auditory nerve., Conclusions: It is important for clinicians to consider the possibility of brain tumors in their differential diagnosis of BMS. Although it is not always easy to eliminate all diseases that may cause an oral burning sensation in patients with BMS-like symptoms, more attention and careful examination based on the patient's psychosomatic background features and other possible causes are needed to rule out organic diseases.

Background: Persistent idiopathic facial pain (PIFP) is the unexplained pain along the territory of the trigeminal nerve, including nonorganic tooth pain called atypical odontalgia (AO). Though PIFP is debilitating to patients' livelihood and well-being, its pathophysiology remains poorly understood. Although neurovascular compression (NVC) of the trigeminal nerve is known to be associated with trigeminal neuralgia (TN), the relationship between NVC and other orofacial pains has not been fully elucidated., Methods: In this study, we investigated the differences in the characteristics of PIFP (primarily AO) patients in the presence or absence of NVC. A retrospective analysis was performed on data from 121 consecutive patients who had been diagnosed with unilateral PIFP according to the criteria of the International Classification of Headache Disorders (ICHD)-3 and underwent magnetic resonance imaging scans of the head., Results: In the group without NVC, characteristic findings were significant for psychiatric morbidity, somatization, and pain disability, when compared with the group with NVC. Furthermore, the group without NVC exhibited significant headache, noncardiac chest pain, shortness of breath, and pain catastrophizing., Conclusions: These results suggest that PIFP patients can be divided into two groups: one consistent with a neuropathic pain phenotype when NVC is present and a functional somatic symptom phenotype when presenting without NVC. Our findings may enable a more precise understanding of pathophysiology of PIFP and lead to better treatment strategies., (© 2020 American Academy of Pain Medicine.)

Objective: To assess the therapeutic dose and safety of amitriptyline and the outcome following treatment with amitriptyline among older patients with burning mouth syndrome (BMS)., Methods: 187 consecutive patients were prescribed amitriptyline as a first-line medication from April 2016 to September 2018 and followed-up for >1 month. Patients were divided into 3 groups: group 1, 113 patients aged <65 years; group 2, 52 patients aged between 65 and 74 years; and group 3, 22 patients aged 75 years or older. The visual analog scale (VAS), Pain Catastrophizing Scale (PCS), Somatic Symptom Scale-8 (SSS-8), Patient Global Impression of Change (PGIC), and Short-form McGill Pain Questionnaire (SF-MPQ) were used for analysis., Results: Thirty-two patients (17 in group 1, 10 in group 2, and 5 in group 3) stopped taking amitriptyline due to side effects. There were no differences among the groups with respect to sex; scores of VAS, PCS, and SSS-8; and drop-out ratio. There were no significant differences in the VAS, PCS, and PGIC scores among the groups after 1 month. The mean daily dose after 1 month was 20.4 ± 8.6 mg in group 1, 17.3 ± 8.7 mg in group 2, and 13.2 ± 5.8 mg in group 3; this difference was significant (p value = 0.003). About 76% of patients showed improvements in their symptoms (PGIC ≥ 3). About 90% of patients reported side effects. No serious side effects occurred., Conclusion: The therapeutic dose of amitriptyline may be lower for older BMS patients than for younger patients., Competing Interests: This work was supported in part by the JSPS KAKENHI (Grant Number 19K10328) awarded to Dr. Toyofuku. The authors report no other conflicts of interest in this work., (© 2019 Suga et al.)

Objectives: There has been considerable research which has focused on clarifying the origin of pain in patients with atypical odontalgia (AO), also known as "idiopathic toothache", and on identifying effective treatment, but there has been limited success so far. In this study, we assessed the outcomes of treatment and attempted to identify factors that could account for pain remission in patients with AO., Patients and Methods: Data for 165 patients diagnosed with AO from June 2015 to August 2017 were retrospectively reviewed. The patients' sex, age, duration of pain, and psychiatric history were collected, along with information on pain intensity, depressive status, and catastrophizing scores. Responses at 4 and 16 weeks from the start of treatment were observed. The associations between potentially associated factors and outcome were investigated using Bayesian model averaging., Results: A 30% reduction in pain was reported by 38 patients (46.3%) at 4 weeks and by 54 patients (65.9%) at 16 weeks. The pain intensity decreased as the depression and catastrophizing score improved; all of the changes were statistically significant ( P <0.001). Four elements, that is, patient sex, depression score at baseline, pain score at 4 weeks, and change in the catastrophizing score, explained 52.5% of the variation in final outcome between individual patients., Conclusion: Our findings confirm the efficacy of tricyclic antidepressants (TCAs) as a treatment for AO and indicate that other medications, especially aripiprazole used in combination with a TCA, may be useful. A considerable number of patients, especially women, those with lower levels of depression at baseline, and those who responded to 4 weeks of treatment, achieved pain relief., Competing Interests: Disclosure The authors have no competing interests to report concerning this study and report no conflicts of interest in this work.

Objective: Oral epithelial cells act not only as mechanical barriers but also as immunological barriers by producing various mediators such as cytokines. Since, in periodontal disease, limited information is available regarding the role of oral epithelial cell-derived cytokines on T cell activation, we investigated the responses of human T cells (Jurkat cell) to cytokines in KB cells (an oral epithelial cell line) that had been stimulated with Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS)., Design: To evaluate T cell activation in response to the culture supernatant of KB cells, we examined cell proliferation and interferon gamma (IFN-γ) production, which is closely related to periodontal disease, in Jurkat cells. Culture supernatant of LPS-stimulated KB cells enhanced cell proliferation and IFN-γ production in Jurkat cells. To determine the active component within the culture supernatant, the production of epithelial cell-derived cytokines, interleukin-12 (IL-12), IL-15 and IL-18, in LPS-stimulated KB cells was analysed., Results: IL-15, but not IL-18, was significantly increased in the culture supernatant of LPS-stimulated KB cells. Moreover, additional anti-IL-15 neutralizing antibody abolished culture supernatant-induced IFN-γ expression in Jurkat cells., Conclusion: These results suggest that periodontal pathogens induce the production of IL-15 from epithelial cells, and leading the activation of T cells in periodontal lesions., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Recent studies have shown that the 15-member macrolide antibiotic azithromycin (AZM) not only has antibacterial activity, but also results in the role of immunomodulator. Interleukin (IL)-8 is an important inflammatory mediator in periodontal disease. However, there have been no reports on the effects of AZM on IL-8 production from human oral epithelium. Therefore, we investigated the effects of AZM on IL-8 production in an oral epithelial cell line., Methods: KB cells were stimulated by Escherichia coli or Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) lipopolysaccharide (LPS) with or without AZM. IL-8 mRNA and protein expression and production in response to LPS were analyzed by quantitative polymerase chain reaction, flow cytometry, and enzyme-linked immunosorbent assay. The activation of nuclear factor-kappa B (NF-κB) and Rac1, which is important for IL-8 expression, was analyzed by enzyme-linked immunosorbent assay and Western blotting, respectively., Results: IL-8 mRNA expression, IL-8 production, and NF-κB activation in LPS-stimulated KB cells were inhibited by the addition of AZM. LPS-induced Rac1 activation was also suppressed by AZM., Conclusions: This study suggests that AZM inhibits LPS-induced IL-8 production in an oral epithelial cell line, in part caused by the suppression of Rac1 and NF-κB activation. The use of AZM might provide possible benefits in periodontal therapy, with respect to both its antibacterial action and apparent anti-inflammatory effect.