Astrocytic and microglial interleukin-1ß mediates complement C1q-triggered orofacial mechanical allodynia.

Glial cells, such as microglia and astrocytes, in the trigeminal spinal subnucleus caudalis (Vc) are activated after trigeminal nerve injury and interact with Vc neurons to contribute to orofacial neuropathic pain. Complement C1q released from microglia has been reported to activate astrocytes and causes orofacial mechanical allodynia. However, how C1q-induced phenotypic alterations in Vc astrocytes are involved in orofacial pain remains to be elucidated. Intracisternal administration of C1q caused mechanical allodynia in the whisker pad skin and concurrent significant upregulation of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 in the Vc. Immunohistochemical analyses clarified that C1q induces a significant increase in the cytokine interleukin (IL)-1ß, predominantly in Vc astrocytes and partially in Vc microglia. The number of c-Fos-positive neurons in the Vc increased significantly in response to C1q. IL-1 receptor antagonist (IL-1Ra) was used to analyze the involvement of IL-1ß in C1q-induced mechanical allodynia. Intracisternal administration of IL-1Ra ameliorated C1q-induced orofacial mechanical allodynia. The present findings suggest that IL-1ß released from activated astrocytes and microglia in the Vc mediates C1q-induced orofacial pain.

The Effectiveness and Adverse Events of Amitriptyline and Aripiprazole in Very Elderly Patients With BMS.

Burning mouth syndrome (BMS) is defined by chronic oral burning sensations without any corresponding abnormalities. Besides amitriptyline, aripiprazole has been reported as a possible medication to manage BMS. However, especially for elderly patients, the adverse events of these medications would be a problem. The aim of the present study was to investigate the differences in the effectiveness and adverse events of amitriptyline and aripiprazole in very elderly patients with BMS. This is a retrospective comparative study of 80 years old and older patients with BMS who were initially treated with amitriptyline or aripiprazole and who were new outpatients of our department from April 2017 to March 2020. All clinical data, including sex, age, comorbid physical diseases, comorbid psychiatric disorders, the prescribed doses (initial, maximum, and effective dose), prognosis, and adverse events, were collected from their medical charts. Each medication was selected considering their medical history. Amitriptyline was prescribed in 13 patients (11 women, 82.3 ± 2.1 years old) and aripiprazole was prescribed in 27 patients (26 women, 84.2 ± 3.8 years old). There were no significant between-group differences in sex, age, duration of illness, pain intensity, salivation, and psychiatric comorbidity at the first examination. Amitriptyline clinically improved more patients (7 patients, 53.8%) with the effective dose of 10 (7.5, 15.0) mg than aripiprazole (11 patients, 40.7%) of which the effective dose was 1.0 (0.5, 1.5) mg, although there were no significant between-group differences. The adverse events of amitriptyline were found in 9 patients (69.2%) and most patients had constipation (46.2%). For aripiprazole, 7 patients (25.9%) showed adverse events, most of them reported sleep disorder (11.1%). Amitriptyline had significantly longer duration taking medication (p = 0.021) and lower discontinuation (p = 0.043) despite of higher occurrence rate of adverse events (p = 0.015) compared to aripiprazole. These results suggest that both psychopharmacotherapies with a low dose of amitriptyline and aripiprazole are effective for the very elderly patients with BMS. Furthermore, aripiprazole may have some advantages in the adverse events compared to amitriptyline; however, the low dose amitriptyline monotherapy may have more benefit in the effectiveness and tolerability over prudent collaboration with primary physicians.

Clinical Characteristics of Predominantly Unilateral Oral Cenesthopathy With and Without Neurovascular Contact.

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.

Personality Traits in Burning Mouth Syndrome Patients With and Without a History of Depression.

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.

Case Report: Iatrogenic Dental Progress of Phantom Bite Syndrome: Rare Cases With the Comorbidity of Psychosis.

Introduction: Phantom bite syndrome (PBS) is considered as the preoccupation with dental occlusion and the continual inability to adapt to changed occlusion. These patients constantly demand occlusal corrections and undergo extensive and excessive dental treatments. We present three cases with PBS-suspected iatrogenic concerns and the attribution to underlying psychosis. Case Presentation: A 70-year-old female demanded orthodontic retreatment and complained of tightness and cramped sensation of teeth in the oral cavity, uncomfortable occlusion, and pain in her neck and legs that she was convinced was induced by orthodontic treatment. However, even earlier than the orthodontic treatment, she had kept doctor shopping for over 35 years, not merely dentists but also psychiatrists, neurologists, and so on; she was diagnosed with bipolar disorder. A 48-year-old female complained of malaligned improper occlusion and demanded occlusal adjustment. These symptoms occurred in the absence of a dental trigger and were worsened by orthodontic treatment. She underwent psychiatric treatment for 15 years with a diagnosis of bipolar disorder. A 38-year-old female, who had a history of schizophrenia for over 20 years, complained of occlusal discomfort and revisited with a complaint of abnormal occlusion due to excessive dental procedures. In the last two cases, requests for dental procedures had reduced owing to the collaboration between the psychiatrists and dentists. All the cases first visited our clinic following a succession of dental visits. They were strongly convinced that occlusal correction was the only solution to their symptoms, including the symptoms of discomfort in other body parts. Their misleading perceptions were uncorrectable, and repeated dental treatments exacerbated their complaints. Moreover, the dentists overlooked the psychotic histories of the patients, while the comorbid psychosis resulted in a strict demand for dental treatment by the patients. Conclusions: The presented PBS cases with psychosis suggest that repeated dental treatments and comorbid psychosis exacerbate PBS. Moreover, their persistent demands reflecting comorbid psychosis led dentists to perform numerous procedures. Early detection of underlying psychosis and the prompt collaboration between psychiatrists and dentists are integral to help prevent complications in PBS cases with psychosis.

Case Report: Hidden Oral Squamous Cell Carcinoma in Oral Somatic Symptom Disorder.

Background: Burning mouth syndrome (BMS) is a common condition of predominant oral pain without evident cause, that maxillofacial surgeons and otolaryngologists often refer to psychiatrists as somatic symptom disorder. In very rare cases, its typical burning symptom mimics those of other diseases in which serious fatal comorbidities may be missed. We encountered three rare cases of oral squamous cell carcinoma (OSCC) with the first symptom of burning tongue. Case Presentation: Case 1: A 68-year-old woman had burning pain on the left lingual margin for 8 years. Antidepressant treatment was not efficacious. Cytology and biopsy revealed OSCC. Case 2: A 70-year-old man had burning sensation and paralysis of the tongue for 6 months. Magnetic resonance imaging (MRI) revealed a 37 × 23-mm mass under the floor of the mouth and enlargement of lymph nodes on both sides. Case 3: A 90-year-old man had burning sensation of the tongue for 1 year. MRI revealed a 12 × 12-mm mass on the mandible with bone absorption. Conclusion: This case series suggests that psychiatrists must always be careful in regarding BMS as somatic symptom disorder and be cautious of the possibility of OSCC, especially in elderly patients.

Differences in the Clinical Characteristics of Persistent Idiopathic Facial Pain (Atypical Odontalgia) Patients with or Without Neurovascular Compression of the Trigeminal Nerve.

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.

Therapeutic Dose of Amitriptyline for Older Patients with Burning Mouth Syndrome.

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.