Purpose: The high prevalence of dementia in the current aging population is causing great strain on nursing and healthcare professionals, and is becoming a major social issue. Cognitive decline reduces independence and diminishes the effectiveness of oral self-care, which makes it difficult to maintain healthy oral and masticatory functions and can increase the risk of orofacial pain. However, the exact relationship between the two is still unknown. The aim of this review article was to explore current problems and future prospects by compiling pre-existing knowledge on the relationship between cognitive impairment, dementia, and orofacial pain.
Study selection: An electronic literature search was performed on PubMed and Ichushi-Web using the keywords “cognitive impairment,” “dementia,” and “orofacial pain.” Since we could only obtain a limited number of original research articles from our online literature search, manual literature search was supplemented.
Results: Some previous reports suggest that the prevalence of orofacial pain is higher in older individuals with cognitive impairment and dementia than in those without these conditions. Contrary to this, other studies report the opposite inference. The diagnosis and prevalence of orofacial pain are considered to be difficult to accurately determine in non-verbal individuals. In addition, current examination and diagnostic procedures for orofacial pain are insufficient for non-verbal individuals with dementia.
Conclusions: In the current unprecedented aging population, establishing accurate diagnostic procedures for orofacial pain in older individuals with dementia should be considered imperative.

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The stellate ganglion is located in front of the transverse process of the C7 vertebra. It is composed of inferior cervical sympathetic ganglion and the first thoracic sympathetic ganglion. The stellate ganglion innervates the head, neck, and upper extremity. Stellate ganglion block （SGB） can dilate blood vessels in the head, neck, and upper extremities, resulting in an increased blood supply. SGB is used for treatment of trigeminal neuropathy, chronic pain conditions like orofacial pain, neuropathic pain.
This review explains the effects of SGB on treatment in dental diseases. The therapeutic effects were evaluated with buccal mucosa blood flow and cheek surface temperature as physiological changes. Buccal mucosa blood flow and cheek surface temperature on SGB side were increased by SGB. Only cheek surface temperature on non SGB side was increased.
The author wants to insist that SGB is an effective therapy for inferior alveolar nerve neuropathy, lingual nerve neuropathy, masticatory muscle pain, neuropathic pain and burning mouth syndrome. About 10 times SGB are necessary for effect judgement.

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Migraine is clinically characterized by recurrent throbbing headache attacks of moderate to severe intensity accompanied by nausea, vomiting, and photophobia/phonophobia. This debilitating and common headache disorder predominantly affects young people and causes an enormous financial burden on society. Although the pathophysiology of migraine remains elusive, it is now appreciated that migraine is primarily a neural disease. Hypothalamic dysfunction seems to be implicated in the emergence of migraine prodrome. Migraine aura is caused by cortical spreading depression/depolarization. Abnormal activation of the trigeminal system is responsible for the generation of migraine headache, wherein calcitonin gene-related peptide （CGRP） plays a pivotal role in provoking peripheral sensitization. Triptans, 5-HT_1B/1D/1F agonists, are the mainstay of migraine acute therapy. It is envisioned that the anti-migraine action of triptans is mediated mainly by inhibition of CGRP release from the trigeminal nerves. For prophylaxis, calcium channel blockers, anti-epileptic drugs, and tricyclic antidepressants are empirically used with a view to rectifying abnormal neural activity. There are unmet needs in the current pharmacological management of migraine. CGRP-targeted therapy, which consists of CGRP-related monoclonal antibodies and small-molecule CGRP receptor antagonists, has recently been launched into migraine management. In particular, CGRP-related antibodies are shown to exert efficacy even in difficult-to-treat cases. We are now entering a new era of migraine treatment.

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Objective: Since masticatory muscle pain is caused by the involvement of multiple factors, there are large individual differences in the duration of illness. Therefore, the purpose of this study was to investigate the psychosocial factors by screening tools whether would influence the duration of illness.
Method: Screening questionnaire for age, gender, and psychosocial factors at the time of diagnosis （Patient Health Questionnaire-9, Patient Health Questionnaire-15 and Generalized Anxiety Disorder-7） from those who were diagnosed with masticatory myalgia and obtained their consent） Score, disease duration （time from onset of subjective symptoms to diagnosis）, and subtype of masticatory muscle pain （local myalgia or myofascial pain）. From the obtained data, the median illness period was calculated. Then, logistic regression analysis was performed with the disease duration （binary variables below and above the median） as the dependent variables and the age, gender, and psychosocial factor scores and the subtype of masticatory muscle pain as the independent variables. We identified the factors that affect the disease duration.
Results: The number of subjects was 68. Patient Health Questionnaire-15 was significant, but other items were not. The odds ratio for Patient Health Questionnaire-15 was 1.25 （95％ Cl 1.09-1.43, p＝0.002）.
Conclusion: The most relevant factor for the duration of illness in patients with masticatory muscles was the PHQ-15 （physical symptom） score.

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Patients：A 74-year-old female has suffered from bilateral upper molar dull pain and temporal headache since 5 years ago．She visited a nearby dental clinic, but no abnormalities were pointed out in the upper jaw. A few months before visiting our hospital, she suddenly noticed dizziness and nausea during dinner, and visited a hospital emergency department. She was diagnosed with Meniere’s disease and dizziness and nausea disappeared. Left temporal headache and left upper molar pain became worse, she was referred to the Department of Pain Clinic in our hospital due to the unexplained paroxysmal orofacial pain. One month after the first consultation, MRI was performed because the paroxysmal pain aggravated. Head MRI showed a space-occupying lesion in the left posterior fossa region. We have referred her to a neurosurgeon. Open surgery of the posterior fossa was performed under general anesthesia. The pain in the left upper molars and temples disappeared. The patient has been followed up without any sequela.
Discussion：The case was diagnosed as chronic headache associated with secondary trigeminal neuralgia due to a giant meningioma in the posterior cranial fossa. Although benign tumors may develop slowly and patients may not present with typical neurologic signs, they sometimes complain of chronic orofacial pain and headaches with neuralgiform symptoms. Dentists should be aware of brain hypertonic signs and should not hesitate to employ screening tests.
Conclusions：If chronic headaches or cranial nerve symptoms are present, dentists should differentially diagnose orofacial pain from secondary headaches or secondary trigeminal neuralgia attributed to intracranial lesions and MRI may be essential to diagnose them.

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Patients: The subject was an 81-year-old man who died of cirrhosis. The left common carotid artery showed a severe tortuosity toward the left lateral side at the height of the fifth to sixth cervical vertebrae. Tortuosity of the vagus nerve and the sympathetic trunk were also noted. These findings suggested that the stellate ganglion block （SGB） procedure might have been difficult to perform. No abnormalities on the right side were noted.
Discussion: In this case, it was difficult to confirm pulsation of the common carotid artery in the normal position through palpation of the sternocleidomastoid muscle. Local anesthetic toxicity due to erroneous intravascular injection seemed to have occurred. Furthermore, although injecting a local anesthetic near the transverse process of the sixth cervical vertebra was possible despite the severe tortuosity of the sympathetic trunk, performing an SGB might not have been successful. The site of predilection of the tortuosity of the carotid artery suspected in this case is normally the right side, but it was observed on the left side, which is extremely rare. Although it is possible to visually recognize anatomical structures such as the common carotid artery with ultrasound guidance, knowledge of cervical anatomy is important.
Conclusion: In this case, tortuosity of the left common carotid artery that could result in a difficult SGB was observed in a cadaver used for anatomical training. When performing SGB, always consider the possibility of potential anatomical deviation and deformation, and if necessary, a careful attitude such as using an ultrasonic guide will lead to patient safety.

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Patient: A 59 -year-old woman was complaining severe pain and dysesthesia in the left premolar region of the maxilla and the left trigeminal nerve branch Ⅱ region. The symptoms suddenly developed after undergoing left maxillary sinus cystectomy 3 years ago. The pain did not improve at all even after visiting various medical institutions. In addition to the appearance of paroxysmal electric shock pain that stings the left trigeminal nerve branch Ⅱ region, persistent pain with throbbing and deep continued throughout the day. At the first visit, we suspected trigeminal nerve pain although it was not typical, and prescribed carbamazepine 100mg/day. The electric shock pain diminished but persistent pain remained. MRI showed neurovascular compression of the trigeminal nerve. In addition, a trigger point with pain related to the left premolar was found in the left temporal muscle, thus the massage guidance was given and the pain was further diminished, however the discomfort and pain with allodynia persisted. After stellate gangrlion blocks （SGB） and Ⅳ magnesium（Mg）sulfate andⅣ lidocaine hydrochloride, the pain subsided within the range of self-control. Currently, the pain is controlled by the combined use of SGB and Ⅳ of Mg and lidocaine.
Discussion: The patient was diagnosed as having both trigeminal neuralgia and complex regional pain syndrome typeⅠwith sympathetically maintained pain, peripheral and central neuropathic pain, and was also concurred myofacial pain.
Conclusion: In the clinical practice of orofacial pain, there are various causes of pain. Careful diagnosis and various approaches are crucial for pain control of such patient.

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Patients: Two cases were patients of twenties （case 1） and fifties （case 2） females, respectively. Their chief complaint was jaw pain, and they were referred to our pain clinic （Nagasaki University Hospital Oral Pain and Liaison Clinic） from general practitioners. Based on the Diagnostic Criteria for Temporomandibular Disorders （DC/TMD） we diagnosed them as arthralgia （type Ⅱ） and masticatory muscle pain （type Ⅰ） of temporomandibular disorders （TMD）, respectively. In the counseling, we found that their symptoms were associated with their own life stresses and assessed them according to the type D of MW classification （psychosomatic disorders （PSD） is obvious）. We managed them based on the psychotherapy.
Discussion: Two patients had stresses and parafunctions like tooth grinding and clenching in common, which might overlord on the joint and the muscle of the jaw, and then cause TMD type Ⅱ and Ⅰ, respectively. Comparing between two cases, the latter had not only pain but also other various symptoms like muscle stiffness, palpitation, and dizziness, which made its management more difficult than the former.
Conclusion: Pathophysiology of TMD is biopsychosocial model, and dual axis diagnosis is recommended. We reported two cases of TMD corresponding to PSD managed by the psychotherapy and add-on therapy.

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Patient: The patient is a 31-year-old female. She had been suffering from burning pain and numbness on the left side of her lower lip and jaw for 2 months. She visited otolaryngology, cerebrovascular medicine, and oral surgery, although the primary disease was not defined and the symptoms did not improve, therefore she was referred to our department. Since the third branch of the left trigeminal nerve region showed pain and sensory disturbance, we started oral administration of VB12, adenosine triphosphate, and mirogabalin, in addition once a week stellate ganglion block treatment. 1 month after the start of treatment, pain and sensory disturbance in the trigeminal region were generally improved, but 4 months after the start of treatment, pain worsened and sensory disturbance spread to all branches of the trigeminal nerve bilaterally. Furthermore, she complained of stiff fingers and pallor of hands in cold environment, which appeared to be Raynaud’s phenomenon, therefore we referred her to rheumatology department. She was diagnosed with mixed connective tissue disease （MCTD） of more than moderate severity, and treatment was initiated. Currently, Raynaud’s phenomenon, arthralgia, and pain in the trigeminal nerve region has improved, but sensory disturbance has remained.
Discussion: Trigeminal neuropathy and trigeminal neuralgia are among the symptoms of MCTD, but there are only a few reports in which these symptoms appeared isolated as initial manifestation prior to frequent symptoms such as Raynaud’s phenomenon, therefore, we had difficulty in diagnosing the primary disease.
Conclusion: MCTD should be considered as a differential diagnosis for pain and sensory disturbances in the trigeminal region.

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Case summary: We report a case of methotrexate-associated lymphoproliferative disease （MTX-LPD） in a 69-year-old woman with rheumatoid arthritis （RA） and Sjögren’s syndrome （SjS） who presented to our department with a complaint of left facial pain. The patient was diagnosed with RA 17 years ago and had been using methotrexate （MTX） and prednisolone for a long time. She also had frequent swelling of the parotid gland due to SjS. The patient had bullae under the left nasal wing and mild swelling of the parotid gland. We diagnosed herpes zoster of the second branch of the left trigeminal nerve and left parotitis caused by SjS, and started the initial treatment. However, neoplastic lesions in the parotid region were suspected, and biopsy results confirmed the diagnosis of MTX-LPD.
Discussion: It is common knowledge that RA and MTX administration are risk factors for the development of stomatitis and herpes zoster. In this case, a patient with repeated swelling of the parotid gland due to SjS came to our hospital with left facial pain, and not only herpes zoster as an acute symptom but also MTX-LPD in the parotid gland area contributed to the difficulty in differential diagnosis.
Conclusion: Patients with autoimmune diseases such as RA and SjS routinely visit dental clinic and oral surgeons, and they often use immunosuppressive drugs such as MTX. When they experience pain in the orofacial region, the condition may be complicated. It is important to consider various differential diseases, such as herpes zoster and malignant lymphoma, and to respond carefully in collaboration with other related departments.

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Patients: The patient is a 76-year-old woman. Two weeks before the first visit to our clinic, we complained of electric shock-like pain in the upper eyelid. She visited an ophthalmologist and was diagnosed as having no abnormalities. Two days later, he was aware of a headache in the right temporal region and facial pain and visited our clinic. At the first visit to our clinic, she complained of electric shock-like pain in the right forehead, temporal region, and occipital region, and head allodynia was observed. In addition, right conjunctival injection, lacrimation, and two pustules were observed on the forehead and tip of the nose. MRI shows that the right trigeminal nerve is not compressed at the root entry zone by the cerebellar artery. A blood test revealed a high VZV antibody titer of 32, suggesting that the patient was diagnosed with the first branch of herpes zoster. For pain management, pregabalin was started at 25mg/day and titrate up as 50mg/day. Three months after the start of pregabalin administration, the headache and facial pain disappeared, so pregabalin was withdrawn.
Discussion: Atypical facial pain and autonomic-like symptoms may develop in acute herpes zoster on the first branch of the trigeminal nerve. It is difficult to distinguish from the first branch of trigeminal neuralgia, Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing（SUNCT）, because its clinical symptoms are similar.
Conclusion: This case presented with various clinical symptoms and was difficult to diagnose. It is necessary for dentists to understand the clinical symptoms necessary for differentiation from the primary headache and painful cranial neuropathies, and to carry out effective examinations and tests.

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Patients: A 40-years-old woman was experienced burning sensation of left lateral side of tongue corresponding to the mandibular left first premolar tooth were appeared．She was prescribed various medicines such as clonazepam, amitriptyline hydrochloride, or pregabalin in the past. However, she could not obtain pain relief. Therefore, she refused to consent to medication. She cared the mandibular left first premolar tooth and frequently touched it. Thus we made the soft type oral appliance. The pain was removed only when she wore it. We examined the screening test for ADHD because of her attitude and pain remained. The test showed that suspicion of ADHD. We refered her to the psychiatrist and she was diagnosed somatic symptom disorder and combined ADHD. Thereby she became to accept medication of the new antidepressant Venlafaxine and obtained pain relief.
Discussion: There are many patients who are suffering from burning mouth syndrome （BMS） for a long time. Sometimes they need to have medical care. This patient was suspected ADHD because of her attitude. Therefore we used screening tools and they showed tendency of ADHD. We refered her to the psychiatrist. This case suggests the importance of screening of ADHD and contact with the psychiatrist to evaluate refractory BMS.
Conclusion: This report suggests that the importance of confirming the screening of ADHD when we examine the patient with burning mouth syndrome.

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The general anesthetic, ketamine, has a long history in the treatment of pain relief at pain clinics. In the past, ketamine was mainly used for neuropathic pain, such as complex regional pain syndrome, postherpetic neuralgia, and phantom limb pain. Recently, however, there has been much interest in the role of ketamine in chronic pain management. We report three cases of chronic pain in the orofacial region that were refractory to various treatments, in whom intravenous ketamine was effective for pain relief.
Patients: The three cases included one each of idiopathic toothache / oral pain, burning mouth syndrome, and myofascial pain syndrome, with a long duration of illness and psycho-social pressure. Since these cases showed refractory to treatments such as drug therapy, nerve block therapy, and physical therapy, intravenous ketamine （0.5mg/kg/40min） was tried and resulted in satisfactory pain relief.
Discussion: Ketamine reduced pain in patients with three different kinds of chronic pain disorders. Pain is an unpleasant personal experience that has both sensory and emotional components. Chronic pain is dominated by an emotional component regulated by the higher brain, such as the anterior cingulate cortex, insular cortex, thalamus, and prefrontal cortex. In our cases, pain relief might have been obtained by the action of intravenous ketamine on the higher brain.
Conclusion: Due to the various side effects of ketamine, great care should be taken during its intravenous administration. In addition, there is very little evidence on the pain relieving effects and adverse effects of ketamine in chronic non-cancer pain. Although further evidence needs to be established through clinical studies based on appropriate protocols, our experience suggests that ketamine could be one of the treatments for orofacial pain that is refractory to various treatments.

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Case: A 60s woman visited to our hospital with symptoms of pain on right maxillary gingiva. There is no redness or swelling on the right maxillary gingiva or palatal mucosa, but allodynia was observed. Computed tomography revealed the right maxilla was rough and no sequestration. The patient had performed heavy ion radiotherapy for right nasal and sinus malignant melanoma （T3N0M0） 10 years ago. There were no findings local recurrence and metastasis of the tumor and radiation osteomyelitis. Thus, we diagnosed neuropathic pain as a late adverse event by ion radiotherapy. Prescription of pregabalin reduced her pain in the maxilla mucosa.
Discussion: There are few reports of late adverse events of ion radiotherapy for nasal, sinus, and head and neck tumors. Peripheral neuropathy may occur as a late adverse event for ion radiotherapy in the patient with nasal, sinus, and head and neck tumors. In this case, protracted neuropathic pain was attenuated by prescription of pregabalin.
Conclusion: We experienced a case with cancer survivorship who has neuropathic pain as a late adverse event of ion radiotherapy. It was managed by analgesic pharmacotherapy.

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Mirogabalin （Tarlige^Ⓡ） has been approved for treating peripheral neuropathic pain; however, there are few clinical reports on its use in the treatment of orofacial pain. We investigated the therapeutic effect and side effects of mirogabalin on traumatic painful trigeminal neuropathy in the orofacial region, which was diagnosed based on the third edition of International Headache Society. Mirogabalin was prescribed to 9 patients with, painful post-traumatic trigeminal neuropathy who visited the Orofacial Pain Clinic of the Nihon University School of Dentistry; we recorded the male: female ratio and the age distribution, symptom duration, therapeutic effect, and side effects among these patients. The therapeutic effects, defined as alleviation in pain and pain intensity, were determined 3 months after mirogabalin was prescribed; the improvement rate for NRS was 40.6 ± 29.0％. Of the 9 cases, 4 reported side effects, namely, somnolence in 3 cases and weight gain and dizziness in one case. In conclusion, although mirogabalin treatment was effective in alleviating traumatic painful trigeminal neuropathy, it also exerted side effects. Therefore, caution should be exerted when using mirogabalin to treat peripheral neuropathy pain in the orofacial region; dose adjustment starting from a low dose is advised.

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Patients: Fifty years old, male. The chief complaint was a pain in the jaw lasted for 10 years. Although he was treated at a university hospital for 5 years, he continued to improve and worsen. His symptoms gradually worsened, and he was unable to eat, so he was transferred to our department. Painless mouth opening range was 25mm and forced opening range was 37mm. Jaw opening and closing pain and spontaneous pain were observed in the masseter muscle. Palpation of the muscles revealed tender pain in the right temporal muscles and bilateral masseter muscles, myofascial pain in the bilateral masseter muscles, and severe pain in the right masseter muscle. The results of psychological testing were high positive for anxiety. The patient was diagnosed with intractable myofascial pain and started treatment. Although the general masticatory muscle pain treatment was ineffective, a stellate ganglion block provided good pain control.
Consideration: This case was intractable myofascial pain for which pain control was difficult for an extended period. Since the stellate ganglion block had an analgesic effect, the pathological condition of this case might be peripheral circulatory disorder of muscles and sympathetically maintained pain.
Conclusion: Stellate ganglion block may improve the pain condition of chronic refractory TMD, whose main condition is myofascial pain. Stellate ganglion block was a valuable treatment for intractable myofascial pain for which satisfactory results were not obtained with the initial treatment of general temporomandibular disorders as in this case.

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Purpose: Conditioned pain modulation （CPM）, temporal summation of pain （TSP） and offset analgesia （OA） are considered to represent the endogenous pain modulation and could be the risk factor of acute and chronic postsurgical pain. The aim was to develop the measurement device for the evaluation of endogenous pain modulation with cold, heat and pressure stimulation.
Materials and methods: The cold and heat stimulating device with Peltier element was controlled by PC. The development environment was Microsoft Visual Studio 2017, and the development language was C#. The setting temperature and measured temperature for CPM, TSP, and OA measurements were displayed in separate windows. Created program was possible to change condition of stimulation such as temperature, and could control temperature between −10 and 50 degrees Celsius. The continuous electronic visual analogue scale （eVAS） for pain and subjective sensation for cold and heat stimulation were also displayed. The results of CPM effect, TSP ratio and OA score in healthy adults were 19.4 （31.8）％, 1.1 （1.1） and 25.5 （40.5）, respectively （median （interquartile range））. 　Discussion: The developed device was a safe and useful measuring instrument for the evaluation of CPM, TSP, and OA which would reflect endogenous pain modulation, in a short time without burdening the subject.
Conclusion: The device for the evaluation of endogenous pain modulation with cold, heat and pressure stimulation was developed.

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