Mirogabalin as a Therapeutic Option for Neuropathic Pain Emerging Post-endodontic Treatment: A Two-case Report.

INTRODUCTION: Occlusal and percussion pain may manifest occasionally following endodontic treatment, influencing retreatment decisions. Two cases of periapical neuropathic pain, classified as post-traumatic trigeminal neuropathic pain according to the International Classification of Orofacial Pain (ICOP), are presented. Although mirogabalin is effective in managing neuropathic pain, there is a lack of clinical reports on its use for occasional post-traumatic trigeminal neuropathic pain after endodontic treatment. These cases highlight clinical symptoms and successful treatment with mirogabalin for post-traumatic trigeminal neuropathic pain after endodontic treatment, providing clinicians a "take-away" lesson for improving patient condition. METHODS: The patients, referred by their primary dentist due to post-endodontic abnormal pain, found no relief with antibiotics or nonsteroidal anti-inflammatory drugs. Although no findings including swelling or periapical radiolucency were observed around the tooth, they experienced occlusal and percussion pain. Local anesthetic testing showed that the pain originated from the peripheral area around the tooth rather than from central sensitization. Dental radiography and cone-beam computed tomography revealed no abnormal findings. Root canal retreatment was performed by a specialist in endodontic treatment. Although endodontic retreatment drastically decreased visual analog scale (VAS) pain score, pain persisted. Based on the ICOP criteria, diseases other than post-traumatic trigeminal neuropathic pain were excluded. Mirogabalin (10 mg/day) was prescribed once daily before bedtime. RESULTS: VAS scores gradually and drastically decreased 2 weeks after mirogabalin therapy. Several months later, no recurrence of post-endodontic pain was observed after tapering off and discontinuing mirogabalin. CONCLUSIONS: These findings suggest the possibility of a new treatment method for post-traumatic trigeminal neuropathic pain after endodontic treatment.

Glossopharyngeal neuralgia due to vertebrobasilar dolichoectasia: a case report.

Glossopharyngeal neuralgia due to vertebrobasilar dolichoectasia is a rare form of neuropathic pain, and presents diagnostic and therapeutic challenges. Clinical presentation: A 67-year-old man presented with severe burning pain in the left oral cavity, with no explanatory findings during dental and ear, nose, and throat evaluations. Temporomandibular joint examination revealed tenderness, and panoramic radiographs showed a noncontributory periapical radiolucency. Magnetic resonance imaging/magnetic resonance angiography revealed abnormally tortuous vertebral arteries compressing the glossopharyngeal nerves and the brainstem. Topical lidocaine reduced pain, confirming glossopharyngeal neuralgia. Carbamazepine was initially ineffective, but at 200 mg pain reduced from 90 to 20 on the visual analog scale. The patient requested and underwent microvascular decompression surgery, which eliminated his pain. Conclusion: When the vertebral artery compresses the glossopharyngeal nerve, the pain is more intense, attributed to its thicker vascular structure. Local anesthetic testing aids in identifying glossopharyngeal neuralgia. Dental practitioners must be skilled in diagnostics and possess anatomical knowledge for accurate evaluation and referral of throat and ear pain.

Sixth cranial nerve palsy and trigeminal neuropathic pain due to a space-occupying lesion.

Various neuropathies of the cranil nerves can accompany trigeminal neuropathic pain attributed to space-occupying lesions. In this case report, the patient presented with persistent intraoral pain and numbness on the right side of the face. Cranial nerve examination revealed dysfunctional eye movements, diplopia, and mechanical hyposensitivity in the mandibular region. The patient was diagnosed with neuropathy due to intracranial lesions and referred to the Department of Neurosurgery and Otorhinolaryngology. The patient was suspected of having malignant lymphoma and is currently undergoing neurosurgical intervention. This article discusses the importance of the examination of the cranial nerve for patients with persistent pain in the trigeminal nerve distribution.

Involvement of interferon gamma signaling in spinal trigeminal caudal subnucleus astrocyte in orofacial neuropathic pain in rats with infraorbital nerve injury.

Background: Trigeminal nerve injury causes orofacial pain that can interfere with activities of daily life. However, the underlying mechanism remains unknown, and the appropriate treatment has not been established yet. This study aimed to examine the involvement of interferon gamma (IFN-γ) signaling in the spinal trigeminal caudal subnucleus (Vc) in orofacial neuropathic pain. Methods: Infraorbital nerve (ION) injury (IONI) was performed in rats by partial ION ligation. The head-withdrawal reflex threshold (HWT) to mechanical stimulation of the whisker pad skin was measured in IONI or sham rats, as well as following a continuous intracisterna magna administration of IFN-γ and a mixture of IFN-γ and fluorocitrate (inhibitor of astrocytes activation) in naïve rats, or an IFN-γ antagonist in IONI rats. The IFN-γ receptor immunohistochemistry and IFN-γ Western blotting were analyzed in the Vc after IONI or sham treatment. The glial fibrillary acid protein (GFAP) immunohistochemistry and Western blotting were also analyzed after administration of IFN-γ and the mixture of IFN-γ and fluorocitrate. Moreover, the change in single neuronal activity in the Vc was examined in the IONI, sham, and IONI group administered IFN-γ antagonist. Results: The HWT decreased after IONI. The IFN-γ and IFN-γ receptor were upregulated after IONI, and the IFN-γ receptor was expressed in Vc astrocytes. IFN-γ administration decreased the HWT, whereas the mixture of IFN-γ and fluorocitrate recovered the decrement of HWT. IFN-γ administration upregulated GFAP expression, while the mixture of IFN-γ and fluorocitrate recovered the upregulation of GFAP expression. IONI significantly enhanced the neuronal activity of the mechanical-evoked responses, and administration of an IFN-γ antagonist significantly inhibited these enhancements. Conclusions: IFN-γ signaling through the receptor in astrocytes is a key mechanism underlying orofacial neuropathic pain associated with trigeminal nerve injury. These findings will aid in the development of therapeutics for orofacial neuropathic pain.

Relationship between burning mouth disorder and gastroesophageal reflux disease: A scoping review.

OBJECTIVE: This study aims to provide a scoping review and attempts to uncover the possible association between burning mouth disorder and gastroesophageal reflux disease. METHODS: PubMed, EMBASE, Web of Science, the Cochrane Library, Ovid, Scopus, and a search platform (EBSCOhost) were searched from their inception to August 22, 2023. RESULTS: After screening 2795 records, 18 articles were included in the final review, comprising cross-sectional studies (n = 9), case-control studies (n = 5), case reports (n = 2), case series (n = 1), and experimental study (n = 1). The prevalence of gastroesophageal reflux disease and its extraesophageal manifestations of laryngopharyngeal reflux in burning mouth patients was reported 3.39%-23.4% and 50%-93.8%, respectively, while oral burning was reported in 9%-45% of patients with gastroesophageal reflux disease. In case-control studies, gastroesophageal reflux disease was more prevalent in patients with burning mouth disorder compared with controls. Burning mouth would be resolved after antireflux therapy in laryngopharyngeal reflux patients in case series. PH value and saliva alternation might be the possible mechanisms. CONCLUSION: The possibility of the correlation between burning mouth disorder and gastroesophageal reflux disease still needs to be clearly demonstrated through better-conducted studies. The link between them is worth to be explored in future research.

Effectiveness of exercise therapy on pain relief and jaw mobility in patients with pain-related temporomandibular disorders: a systematic review.

Background: Orofacial pain conditions are complex disorders that involve biological, social, and psychological factors. Temporomandibular Disorders (TMDs) are one of the most common orofacial pain conditions, and our previous literature review indicated that exercise therapy has shown promise in reducing TMD-related pain. However, more evidence is needed to firmly establish its effectiveness. Objectives: This systematic review aims to investigate the effectiveness of exercise therapy on pain relief and jaw mobility in patients with pain-related TMDs. Methods: To include randomized controlled trials (RCTs) written in English, a literature search was performed using PubMed, Scopus, Web of Science, Cochrane Library, Ovid, EBM reviews, and Academic Search Complete initially from 4th November 2020 until March 2022. A PICOS for this review was as follows; P: Patients with TMD myalgia or arthralgia, I: Excursion exercise, Stretch exercises, Resistance exercise, or Coordination exercise, C: No treatment or education only. O: Pain intensity and Range of Motion (ROM), S: RCTs. After title screening, a full-text assessment was done to extract data. According to Risk of Bias (RoB) 2.0, risk of bias was assessed in each included paper by 2 reviewers independently. Results: A total of 3,388 titles were identified from the electronic database search. After the screening and full-text evaluation, only 5 studies (145 participants) were eligible to be included. Among the exercise modalities, coordination exercise showed a significant effect on pain relief and improvement of joint mobility. Discussion: Due to the heterogeneity and small sample size of the included studies, a meta-analysis was not feasible. However, this systematic review suggested that exercise therapy, especially coordinate exercise, can be effective in managing painful TMD conditions. Further research is needed to establish optimal parameters for this patient population, as well as standardization and consistency in terminology and treatment structure.

Post-Traumatic Trigeminal Neuropathic Pain after Dental Implant Surgery and the Injustice Experience Questionnaire.

Painful post-traumatic trigeminal neuropathy (PTTN) is a known complication of dental implant therapy. Patients with PTTN develop sensory abnormalities in the orofacial region, which may be a psychosocial aspect, and dentists should assess somatosensory testing and psychosocial factors. The patients were assessed using quantitative sensory testing (QST). A 64-year-old female presented with allodynia of the left lower lip that occurred after a surgical implant procedure. Persistent pain started 4 months after the placement of two dental implants in the mandible. Sensory testing of these areas revealed warm hyposensitivity and mechanical hypersensitivity of the mandibular region. We also assessed PTTN-related perceived injustice using the Injustice Experience Questionnaire. The patient refused medication therapy such as pregabalin; therefore, autogenic training was adopted as an alternative management strategy. We conclude that for expensive dental procedures, such as implant placement, sufficient consensus should be obtained preoperatively before proceeding with surgery.

Chronic osteomyelitis mimicking a temporomandibular disorder: a case report of two cases.

Chronic osteomyelitis of the jaw is rare in the healthy populations of developed countries and presents with diagnostic and therapeutic challenges. Clinical presentation: Patient 1 presented with a dull, occasionally throbbing pain in the left mandible of 1.5 years duration. There was associated trismus which alternated between improving and worsening. The patient had features mimicking a variant of temporomandibular disorder (TMD). She was misdiagnosed and treated for myogenous TMD without symptom relief. Patient 2 presented with intermittent dull pain with mastication and facial swelling over the right mandible for 1 year. She was treated by the referring dental practitioner for myogenous TMD without symptom relief. Clinical and radiologic findings confirmed a diagnosis of chronic sclerosing osteomyelitis in both cases, and conservative treatment, including antibiotics, relieved the pain with no signs of recurrence. Conclusion: The importance of including chronic osteomyelitis in the differential diagnosis of idiopathic orofacial pain disorders is emphasized. If the management of myogenous TMD is unsuccessful, there is a possibility of a misdiagnosis, and a differential diagnosis, including chronic osteomyelitis, needs to be reconsidered.

Trigeminal Neuralgia With Concomitant Continuous Pain Due to Vertebrobasilar Dolichoectasia: A Case Report.

This passage discusses a case of trigeminal neuralgia (TN) with continuous pain and hemifacial spasm caused by vertebrobasilar dolichoectasia, a rare condition. The patient experienced ongoing orofacial pain, which initially led to dental treatments. After unsuccessful medication (carbamazepine), the patient underwent microvascular decompression to alleviate nerve compression by the elongated vertebral artery. This report highlights the challenge of treating such cases due to the unique nature of neurovascular compression. Additionally, it introduces the concept of TN with concomitant continuous pain and emphasizes the need for comprehensive diagnosis, as vertebrobasilar artery elongation is associated with various symptoms, including TN and hemifacial spasms.

Infective Endocarditis With Secondary Headache: A Case Report.

Secondary headache is a symptom of an underlying disease. Infective endocarditis (IE) is a serious infection of the heart tissue. Herein, we present a rare case of IE, with a secondary headache. The patient presented with persistent headache, fever of 39°C, myalgia, and painful erythema of the plantar surface of the foot. The headache progressively worsened over a few weeks. She was diagnosed with secondary headache, and sepsis was suspected. Blood culture revealed the presence of Streptococcus viridans, leading to a diagnosis of IE. Postoperatively, the patient recuperated without any complications. Headaches can be secondary to other conditions. Therefore, comprehensive assessment and accurate diagnosis are essential. Dentists must be aware that headache is a concomitant symptom of IE.

Trigeminal Herpes Zoster Transited to Ipsilateral Occipital Neuralgia.

The pain of occipital neuralgia (ON) is thought to be secondary to trauma or injury to the occipital nerve at any point along the course of the nerve. ON may also be caused by an infectious process (herpes zoster) or compression of the nerve. The patient, in this case, presented to our clinic with complaints of occipital pain and rash and swelling of the right lower jaw. One week before presenting to our clinic, the patient developed severe pain in the first division of the trigeminal region with erythema and vesicles. A blood test showed a remarkably high antibody titer for varicella-zoster virus (VZV). The patient was prescribed oral valacyclovir (Valtrex®) (3000 mg/day), which resulted in the complete remission of the rash and blisters in the occipital region. This highlights the importance of considering neuroanatomy of the trigeminal region and cervical nerve.

Association Between Anxiety and Descending Pain Modulation of Thermal Stimuli in Patients with Burning Mouth Syndrome: A Cross-Sectional Study.

AIMS: To investigate the predictive power of depression and anxiety for conditioned pain modulation (CPM) and to examine the relationships of CPM at 40°C and CPM at 47°C with age, disease-related pain, pain duration, and psychosocial factors in burning mouth syndrome (BMS). METHODS: A total of 22 patients with BMS and 22 healthy female controls participated in this study. Temporal summation was used as the test stimulus for CPM, and subsequent exposure either to a nonpainful (40°C) or a painful (47°C) Peltier thermode was used as the conditioning stimulus. CPM was calculated as the difference in pain perception following the conditioning stimulus. Psychosocial factors were examined using the Profile of Mood States (POMS) and the State-Trait Anxiety Inventory (STAI). RESULTS: State anxiety and tension-anxiety scores were significantly higher for patients with BMS than for control participants. Multiple regression analyses showed that CPM47°C was affected by vigor, fatigue, confusion, and trait anxiety (adjusted R2 = 0.685, F = 5.147, P = .098). The corresponding analysis for CPM40°C showed that the model was not predictive for the following variables: disease-related pain, pain duration, or components of the POMS or STAI. A significant positive correlation was found between CPM47°C and trait anxiety, suggesting that trait anxiety negatively affected the endogenous pain modulation system. CONCLUSION: Increases in trait anxiety reduced the CPM effect. These findings suggest that CPM impairments and increases in trait anxiety are involved in the development of BMS.

Potential differences in somatosensory function during premenopause and early and late postmenopause in patients with burning mouth syndrome: An observational case-control study.

BACKGROUND/PURPOSE: Burning mouth syndrome (BMS) is a chronic condition presenting as intraoral burning or dysesthesia, with a high preponderance in menopausal women. This study aimed to examine the association between somatosensory dysfunction and BMS in premenopausal, early postmenopausal, and late postmenopausal patients, using a standardized Quantitative Sensory Testing (QST) protocol, and to determine the predictive value of thermal or mechanical perception by QST for detecting BMS. MATERIALS AND METHODS: An observational case-control study was performed with 36 female participants with BMS (12 premenopausal, 10 early postmenopausal, and 14 late postmenopausal) and 42 age- and sex-matched healthy volunteers (21 premenopausal, 10 early postmenopausal, and 11 late postmenopausal). Neurophysiological tests were used to evaluate somatosensory dysfunction at the tongue. RESULTS: Z-score in the late postmenopausal BMS group revealed a gain of function for the cold pain threshold and heat pain threshold (Z = 2.08 and 3.38, respectively). In the multiple regression analysis with the Visual Analog Scale as the dependent variable, the vibration detection threshold predicted the severity of burning mouth sensation in the premenopausal group. CONCLUSION: Late postmenopausal patients with BMS showed an increased response of the tongue to noxious thermal stimuli. This supports the theory that changes in sex hormones may affect trigeminal somatosensory function, particularly during the late postmenopausal stage in patients with BMS.

Headache Attributed to Temporomandibular Disorder and Primary Cough Headache.

Orofacial pain is a frequent chief complaint of many systemic disorders. A primary cough headache may mimic the clinical symptoms of a temporomandibular disorder (TMD) or may be associated with TMDs. Case report: A 52-year-old man presented with a 1-year history of TMD symptoms with clicking. He presented with the chief complaint of a sudden and severe headache when coughing, sneezing, or crouching. Comprehensive intra- and extra-oral examinations were performed, which revealed myofascial pain involving the right masseter and temporalis muscles, disc displacement with reduction in the right temporomandibular joint, and headache attributed to TMD, but no severe headaches appeared in the cough-induced test at the first visit. Initially, we advised the patient to minimize activities that require jaw function (e.g., chewing), avoid jaw parafunction (e.g., bruxism), and to perform at-home jaw exercises to stretch the jaw muscles. The patient's symptoms reduced by more than half after the TMD home care and physiotherapy. He was then treated with 75 mg of indomethacin per day, which eliminated his headache. The patient was then referred to a headache specialist, who diagnosed primary cough headache.

Worldwide prevalence estimates of burning mouth syndrome: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the worldwide prevalence and epidemiology profile of burning mouth syndrome. MATERIAL AND METHODS: A systematic review and meta-analysis was conducted. Search strategies were performed in PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang database for studies published before January 31, 2021, for the prevalence of burning mouth syndrome. RESULTS: Eighteen articles were included. The overall pooled prevalence of burning mouth syndrome was 1.73% (95% CI = 0.176-0.351, n = 26,632) in general population, and 7.72% (95% CI = 0.434-0.691, n = 86,591) in clinical patients. The subgroup analysis by continent showed that among the population-based studies the prevalence in Asia (1.05%) lower than in Europe (5.58%) and North America (1.10%). The subgroup analysis by gender showed the prevalence of female (1.15%) was higher than male (0.38%) in general population. The subgroup analysis by age showed the prevalence was higher for people over 50 (3.31%) than under 50 (1.92%). CONCLUSIONS: The pooled prevalence of burning mouth syndrome was relatively high in both general population and clinical patients, varies in different regions with the highest prevalence in Europe, and females over 50 years were the most susceptible group. More epidemiological surveys on the prevalence of burning mouth syndrome are needed.

Diagnostic Tool Using the Diagnostic Criteria for Temporomandibular Disorders: A Randomized Crossover-Controlled, Double-Blinded, Two-Center Study.

AIMS: To assess the speed and accuracy of a checklist user interface for the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). METHODS: A diagnostic tool formatted as a checklist was developed and compared to an existing diagnostic tool, the DC/TMD diagnsostic decision trees. Both types of tools use the DC/TMD and were tested by dental students, interns, and residents in the USA and Japan for diagnosis of hypothetical patients. The comparisons were done in a randomized, crossover, controlled, double-blinded trial. RESULTS: Overall, subjects using the experimental tool answered 25% more correct diagnoses (P < .001) and missed 27% fewer diagnoses (P < .01). They were also able to finalize their diagnoses faster than those using the control tool, in 16% less time (P < .05). The difference in accuracy was more pronounced in complex cases, while the difference in speed was more pronounced in simple cases. CONCLUSION: This checklist is an alternative user interface for the DC/TMD.

Unilateral Trigeminal Sensory Neuropathy with Sjögren's Syndrome with Liver and Renal Impairment.

Liver and renal involvement is a rare event in Sjögren's syndrome. Sjögren's syndrome is characterized by the progressive immune-mediated destruction of epithelial tissues of the salivary and lacrimal glands. Sensory ganglionitis, accompanied by T-cell invasion, occurs in patients with Sjögren's syndrome, resulting in sensory neuropathy of the face or limbs. Patients are assessed by quantitative sensory testing. A 76-year-old woman presented with numbness of her left face and was subsequently diagnosed with Sjögren's syndrome and primary biliary cirrhosis, and was found to have renal failure. Detection of her serum anti-Ro/SSA antibody was strongly positive. Shirmer's test or a salivary volume in the gum test also showed positive results. Her somatosensory disturbance severity was higher in the trigeminal area than in the forearm, suggesting that the trigeminal nerve is more susceptible than other parts of the nervous system in patients with Sjögren's syndrome and primary biliary cirrhosis. A simple sensory test could be performed during regular check-ups, as sensory deficits might develop after patients are diagnosed with Sjögren's syndrome and primary biliary cirrhosis.

Altered somatosensory processing in secondary trigeminal neuralgia: A case report.

Secondary trigeminal neuralgia might be very rarely preceded by trigeminal neuropathic pain. The patient, in this case, presented with paroxysmal pain in the left mandible and numbness of the lower lip and tongue. Sensory testing of these areas revealed cold and heat hyperalgesia and mechanical hyposensitivity in the mandibular region. Magnetic resonance imaging showed a mass in the left cerebellopontine angle. The patient was prescribed systemic mirogabalin (2.5 mg/day), which provided some relief until the tumor was removed. The histopathological diagnosis was an epidermoid tumor. This article discusses the clinical characteristics and sensory testing findings that distinguish secondary trigeminal neuralgia from trigeminal neuropathic pain based on the International Classification of Orofacial Pain.

Orofacial Neuropathic Pain-Basic Research and Their Clinical Relevancies.

Trigeminal nerve injury is known to cause severe persistent pain in the orofacial region. This pain is difficult to diagnose and treat. Recently, many animal studies have reported that rewiring of the peripheral and central nervous systems, non-neuronal cell activation, and up- and down-regulation of various molecules in non-neuronal cells are involved in the development of this pain following trigeminal nerve injury. However, there are many unknown mechanisms underlying the persistent orofacial pain associated with trigeminal nerve injury. In this review, we address recent animal data regarding the involvement of various molecules in the communication of neuronal and non-neuronal cells and examine the possible involvement of ascending pathways in processing pathological orofacial pain. We also address the clinical observations of persistent orofacial pain associated with trigeminal nerve injury and clinical approaches to their diagnosis and treatment.