Pharmacotherapeutic outcomes in atypical odontalgia : determinants of pain relief

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

Burning Mouth Syndrome and Atypical Odontalgia

Objective: This study aimed (1) to investigate the differences in clinical characteristics of patients between 2 groups, those who have atypical odontalgia (AO) only and those who have AO with burning mouth syndrome (BMS), and (2) to assess the influence of psychiatric comorbidity factors on patients' experiences. Method: Medical records and psychiatric referral forms of patients visiting the Psychosomatic Dentistry Clinic of Tokyo Medical and Dental University between 2013 and 2016 were reviewed. The final sample included 2 groups of 355 patients: those who have AO only (n = 272) and those who have AO with BMS (AO-BMS; n = 83). Clinicodemographic variables (gender, age, comorbid psychiatric disorders, and history of headache or sleep disturbances) and pain variables (duration of illness, pain intensity, and severity of accompanying depression) were collected. Initial pain assessment was done using the Short-Form McGill Pain Questionnaire, and depressive state was determined using the Zung Self-Rating Depression Scale. Results: The average age, female ratio, and sleep disturbance prevalence in the AO-only group were significantly lower than those in AO-BMS group. AO-BMS patients rated overall pain score and present pain intensity significantly higher than did the AO-only patients (P = 0.033 and P = 0.034, respectively), emphasizing sharp (P = 0.049), hot-burning (P = 0.000), and splitting (P = 0.003) characteristics of pain. Patients having comorbid psychiatric disorders had a higher proportion of sleep disturbance in both groups and a higher proportion of depressive state in the AO-only group. Conclusions: AO-BMS patients have different epidemiological characteristics, sleep quality, and pain experiences compared to AO-only patients. The presence of psychiatric comorbidities in both groups may exacerbate sleep quality. We suggest that BMS as a comorbid oral disorder in AO patients contributes to a more intensively painful experience

Neurovascular Compression in Atypical Odontalgia Patients

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

Psychiatric comorbidities in patients with Atypical Odontalgia

Objective: Atypical Odontalgia (AO) is a condition characterized by tooth pain with no apparent cause. Although psychiatric comorbidity seems to be very common, it has rarely been studied. To clarify the influence of psychiatric comorbidity on the clinical features in patients with AO, we retrospectively evaluated their examination records. Methods: Clinical features and psychiatric diagnoses of 383 patients with AO were investigated by reviewing patients' medical records and referral letters. Psychiatric diagnoses were categorized according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). We also analyzed visual analogue scale (VAS), self-rating depression scale (SDS), and the short-form McGill pain questionnaire (SF-MPQ) scores. Results: Of the 383 patients with AO, 177 (46.2%) had comorbid psychiatric disorders. The most common were depressive disorders (15.4%) and anxiety disorders (10.1%). Serious psychotic disorders such as bipolar disorder (3.0%) and schizophrenia (1.8%) were rare. Dental trigger of AO was reported in 217 (56.7%) patients. There were no significant correlations between psychiatric comorbidities and most of the demographic features. Higher VAS and SDS scores, higher frequency of sleep disturbance, and higher ratings of “Fearful” and “Punishing-cruel” descriptors of the SF-MPQ were found in patients with psychiatric comorbidity. Conclusions: About half of AO patients had comorbid psychiatric disorders. Dental procedures are not necessarily causative factors of AO. In AO patients with comorbid psychiatric disorders, pain might have a larger emotional component than a sensory one. VAS, SDS, and SF-MPQ scores might aid in the noticing of underlying comorbid psychiatric disorders in AO patients

Comorbid depressive disorders and left-side dominant occlusal discomfort in patients with phantom bite syndrome

Background: Phantom bite syndrome (PBS) is characterised by occlusal discomfort without corresponding dental abnormalities. Despite repeated, failed dental treatments, patients with PBS persist in seeking bite correction. PBS has been regarded as a mental disorder. However, we have reported that PBS patients with a dental trigger tend to have less psychiatric history than those without. Hence, the symptoms of PBS cannot be explained by a mental disorder alone, and it is unclear if mental disorders affect occlusal sensation. Objective: To elucidate the pathophysiology of PBS, we analysed the dental history, PBS symptom laterality and psychiatric history of patients. Methods: In this retrospective study, we reviewed outpatients with PBS who presented at our clinic between April 2012 and March 2017. Their medical records were reviewed for demographic data, medical history and laterality of occlusal discomfort. Results: Approximately half of the 199 enrolled patients had bilateral occlusal discomfort. In the others, the side with occlusal discomfort generally tended to be the one that had received dental treatment. There was no significant relationship between the side chiefly affected by occlusal discomfort and whether dental treatment had been received; however, the affected side differed depending on whether the patient had comorbid psychiatric disorders (P = .041). Conclusions: The distributions of the side with symptoms of PBS were different between those with and without comorbid psychiatric disorders, suggesting that psychiatric disorders might affect occlusal sensation due to a subtle dysfunction in brain areas central to sensory integration. Central dysfunction might play an important role in PBS

Retrospective chart review of oral somatic delusions

Objective: Oral cenesthopathy is characterized by foreign body sensations without medical and dental evidence for them. It is thought to be a rare disease in psychiatry, but many patients are visiting dental clinics seeking treatment to remove a foreign body. Even though the features of oral cenesthopathy might be different between a psychiatric clinic and a dental clinic, there has been no clinico-statistical study from dentists. In this study, we report a clinico-statistical study of patients with oral cenesthopathy in dentistry. Methods: This is a retrospective chart review of 606 outpatients with oral cenesthopathy in Tokyo Medical and Dental University from April 2010 through to March 2015. Results: A total of 159 male and 447 female patients were included in this study. The mean age was 62.08 years, and female patients were older than male patients. The trigger of the dental treatment and the acute phase of depression at the onset were significantly related (p=0.037). Only 128 patients (36%) had clinically significant improvement after 6 months of pharmacotherapy. No history of psychiatric disorders (odds ratio [OR] 0.479 [95% confidence interval {CI}: 0.262–0.875], p=0.017) and longer duration of illness (>18 months) (OR 2.626 [95% CI: 1.437–4.799], p=0.002) were significant factors for clinical outcomes. Conclusion: Patients with oral cenesthopathy in our clinic were predominantly elderly female patients. Dental treatment in the acute phase of depression might be a risk factor for oral cenesthopathy. Therefore, comprehending the situation of psychiatric disorder and obtaining adequate informed consent might be required to prevent the trouble concerning oral cenesthopathy

転移・再発乳癌患者に対するエリブリン療法の有用性

　エリブリンはタキサンとは異なる作用機序をもつ微小管阻害剤である．海外の第Ⅲ相試験 では，エリブリンの転移・再発乳癌に対する延命効果が示されている．今回，エリブリンの臨床 的な有用性を検討するため，2011年９月から2017年８月に当科でエリブリン療法を行った進行・ 再発乳癌97症例を対象として後方視的に調査した．対象患者の年齢は35 － 81歳（中央値58）， performance status は１が最多で64例，Stage Ⅳが５例，再発が92例であった．原発腫瘍のエス トロゲン受容体は陽性が64例，プロゲステロン受容体は陽性が48例，human epidermal growth factor receptor 2は陰性が78例であった．前化学療法のレジメン数は0 － 9（中央値２）, 臓器転 移ありが69例，肝転移ありが40例，エリブリン療法の実施サイクル数は1 － 12回（中央値3.5）， 観察期間は1 － 55か月（中央値10），有害事象による中止例は10例であった．最大治療効果は，完 全奏効が０例，部分奏効が１例，長期安定が27例，安定が16例，進行が42例，不明・評価不能が 11例であった． 臨床的有効率（奏効率＋長期安定率）は29% であった．Time-to-treatment failure (TTF) は0 － 178週間（中央値13），治療開始後全生存期間は0 － 55か月（中央値15.5）であった． 好中球減少症はグレード１が最多で61例，非血液毒性は嘔気が７例，肝機能障害が６例，末梢神 経障害が５例，間質性肺炎が3例などであった．良好なTTF の予測因子は，単変量解析で「臓器転 移なし」（P = 0.0356）が同定された．良好な治療開始後生存の予測因子は，多変量解析にて「臨 床的有効性あり」（P = 0.0008）と「PS が０か１」（P < 0.0001）が同定された．エリブリン療法は， 奏効率は低かったが，本療法は，約30% の症例に臨床的有効性をもたらし，生存期間の延長に寄 与する可能性がある．　Eribulin is an anti-microtubule agent that uses a different mechanism of action to taxanes. Phase 3 clinical trials have shown that eribulin exerts life-prolonging effects in patients with metastatic or recurrent breast cancer. In order to investigate the utility of eribulin, we conducted a retrospective and observational study on 97 patients with metastatic and recurrent breast cancer who were treated in our institute between September 2011 and August 2017. The median age of the patients was 58 years (range: 35 － 81). The performance status was 1 in 64 patients. Five patients had stage IV disease, while 92 had recurrent disease. Sixtyfour patients had estrogen receptor-positive tumors, 48 had progesterone receptor-positive tumors, and 78 had human epidermal growth factor receptor 2-negative tumors. The median number of regimens of previous chemotherapies was 2 (range: 0 － 9). Sixty-nine patients had visceral metastases, while 40 had liver metastases. The median number of cycles of eribulin therapy was 3.5 (range: 1 － 12). The median follow-up period was 10 months (range: 1 － 55). The best responses to therapy were a complete response in 0 patients, a partial response in 1, long-term stable disease in 27, stable disease in 16, progressive disease in 42, and unevaluable in 11. The clinical benefit rate (objective response rate + long-term stable disease rate) was 32%. The median time-to-treatment failure (TTF) was 13 weeks (range: 0 － 178). Median overall survival (OS) after the initiation of therapy was 15.5 months (range 0 － 55). The most frequent grade of neutropenia was 1, which was observed in 61 patients. Major non-hematological toxicities were nausea in 7 patients, liver dysfunction in 6, peripheral neuropathy in 5, and interstitial pneumonitis in 3. Univariate and multivariate analyses identified “no visceral metastasis” as the only predictive factor for TTF (P = 0.0356 for the multivariate analysis). The multivariate analysis revealed that“ the presence of a clinical benefit by the therapy” (P = 0.0008) and “a performance status of 0 or 1” (P < 0.0001) were independent predictive factors for OS. Eribulin therapy for patients with metastatic or recurrent diseases provided clinical benefits for approximately 30% of patients. These results suggest that this therapy prolongs the OS of patients

センチネルリンパ節生検を施行した腋窩リンパ節微小転移乳癌症例の検討

N0乳癌において症例を選べば，センチネルリンパ節転移陽性例であっても，腋窩リンパ節郭清（ALND）の省略が可能であると報告されている．微小転移（pN1mi）乳癌においても，同様の結果が得られている．当科でセンチネルリンパ節生検（SLNB）を施行し，pN1mi であった66例を研究対象とした．SLNB の方法は，99mTc-フチン酸を用いたRI 法とインドシアニングリーンを用いた色素法の併用法で行った．SLNB 群52例とSLNB → ALND 群14例に分け，予後を中心に検討し，ALND 省略の可能性について検討した．結果は，１）SLNB 群とSLNB → ALND 群で無病生存率および全生存率に有意差を認めなかった．２）乳房切除症例でも同様の結果であった．３）スキップ症例や術後にpN1mi と判明する症例が存在する．pN1mi 症例では乳房の術式にかかわらずALND の省略が可能である．It has been reported that axillary lymph node dissection (ALND) can be safely omitted if we carefully select breast cancer patients with sentinel lymph node metastases, including breast cancer patients with micrometastases (pN1mi). The subjects were 66 breast cancer patients with pN1mi who underwent sentinel lymph node biopsy (SLNB) in our department. SLNB was performed by the dual method using 99mTc-phytate and indocyanine green. We divided the subjects into the SLNB group (n=52) and SLNB → ALND group (n=14). Clinico-pathological factors, in particular prognosis of the patients were retrospectively studied. 1) No significant difference in disease-free survival and overall survival between the SLNB → ALND group and the SLNB group. 2) The similar findings were observed in patients who underwent mastectomy. 3) The pN1mi patients consisted of patients with so-called skip metastases and patients whose micrometastases were found in permanent sections after surgery. The omission of ALND is possible regardless of surgical methods, i.e., mastectomy or breast-conserving surgery, in pN1mi patients

Increase in IGF-1 Expression in the Injured Infraorbital Nerve and Possible Implications for Orofacial Neuropathic Pain

Insulin-like growth factor-1 (IGF-1) is upregulated in the injured peripheral nerve bundle and controls nociceptive neuronal excitability associated with peripheral nerve injury. Here, we examined the involvement of IGF-1 signaling in orofacial neuropathic pain following infraorbital nerve injury (IONI) in rats. IONI promoted macrophage accumulation in the injured ION, as well as in the ipsilateral trigeminal ganglion (TG), and induced mechanical allodynia of the whisker pad skin together with the enhancement of neuronal activities in the subnucleus caudalis of the spinal trigeminal nucleus and in the upper cervical spinal cord. The levels of IGF-1 released by infiltrating macrophages into the injured ION and the TG were significantly increased. The IONI-induced the number of transient receptor potential vanilloid (TRPV) subfamily type 4 (TRPV4) upregulation in TRPV subfamily type 2 (TRPV2)-positive small-sized, and medium-sized TG neurons were inhibited by peripheral TRPV2 antagonism. Furthermore, the IONI-induced mechanical allodynia was suppressed by TRPV4 antagonism in the whisker pad skin. These results suggest that IGF-1 released by macrophages accumulating in the injured ION binds to TRPV2, which increases TRPV4 expression in TG neurons innervating the whisker pad skin, ultimately resulting in mechanical allodynia of the whisker pad skin