• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.45 no.5
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• pp.233-240
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• 2019

Trigeminal nerve injury as a consequence of lower third molar surgery is a notorious complication and may affect the patient in long term. Inferior alveolar nerve (IAN) and lingual nerve (LN) injury result in different degree of neurosensory deficit and also other neurological symptoms. The long term effects may include persistent sensory loss, chronic pain and depression. It is crucial to understand the pathophysiology of the nerve injury from lower third molar surgery. Surgery remains the most promising treatment in moderate-to-severe nerve injuries. There are limitations in the current treatment methods and full recovery is not commonly achievable. It is better to prevent nerve injury than to treat with unpredictable results. Coronectomy has been proved to be effective in reducing IAN injury and carries minimal long-term morbidity. New technologies, like the roles of erythropoietin and stem cell therapy, are being investigated for neuroprotection and neural regeneration. Breakthroughs in basic and translational research are required to improve the clinical outcomes of the current treatment modalities of third molar surgery-related nerve injury.

• International Journal of Oral Biology
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• v.45 no.3
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• pp.84-91
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• 2020

The present study investigated the participation of D-serine and NR2 in antinociception produced by blockade of central erythropoietin-producing hepatocellular carcinoma (Eph) A4 (EphA4) signaling in rats with trigeminal neuropathic pain. Trigeminal neuropathic pain was modeled in male Sprague-Dawley rats using mal-positioned dental implants. The left mandibular second molar was extracted under anesthesia, and a miniature dental implant was placed to induce injury to the inferior alveolar nerve. Our current findings showed that nerve injury induced by malpositioned dental implants significantly produced mechanical allodynia; additionally, the inferior alveolar nerve injury increased the expression of D-serine and NR2 subunits in the ipsilateral medullary dorsal horn (trigeminal subnucleus caudalis). Intracisternal administration of EphA4-Fc, an EphA4 inhibitor, inhibited nerve injury-induced mechanical allodynia and upregulated the expression of D-serine and NR2 subunits. Moreover, intracisternal administration of D-amino acids oxidase, a D-serine inhibitor, inhibited trigeminal mechanical allodynia. These results show that D-serine and NR2 subunit pathways participate in central EphA4 signaling after an inferior alveolar nerve injury. Therefore, blockade of D-serine and NR2 subunit pathways in central EphA4 signaling provides a new therapeutic target for the treatment of trigeminal neuropathic pain.

• Journal of Dental Anesthesia and Pain Medicine
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• v.19 no.2
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• pp.77-82
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• 2019

It is well known that trigeminal nerve injury causes hyperexcitability in trigeminal ganglion neurons, which become sensitized. Long after trigeminal nerve damage, trigeminal spinal subnucleus caudalis and upper cervical spinal cord (C1/C2) nociceptive neurons become hyperactive and are sensitized, resulting in persistent orofacial pain. Communication between neurons and non-neuronal cells is believed to be involved in these mechanisms. In this article, the authors highlight several lines of evidence that neuron-glial cell and neuron macrophage communication have essential roles in persistent orofacial pain mechanisms associated with trigeminal nerve injury and/or orofacial inflammation.

• Journal of Oral Medicine and Pain
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• v.40 no.1
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• pp.35-40
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• 2015

Purpose: This study aims to assess the psychological characteristics of patients with iatrogenic damage of the trigeminal nerve using Symptom Checklist-90-Revised (SCL-90-R). Methods: A total of 22 patients who visited the clinic of Department of Oral Medicine, School of Dentistry, Chosun University were evaluated in the months from December 2012 to December 2014. Patients were included in the study if they presented with reported sensory changes due to iatrogenic trigeminal nerve injury. A total of 37 control group who has no symptoms of pain and sensory change were included in the study. All participants filled out the SCL-90-R instrument to assess psychosocial symptoms. Results: The T-scores of most of the SCL-90-R symptom dimensions were within normal range (less than 55) in the patients and the control group. The patients group showed higher T-scores of SCL-90-R than those of the control group, with statistically significance of somatization, anxiety, psychoticism, and positive symptoms distress. Female patients group had higher Tscores of SCL-90-R than those of male patients group, but there was no statistical difference, except for the positive symptom global index. The chronic patients group showed higher Tscores of SCL-90-R than those of the acute patients group, but there was no statistical difference, except for the Positive symptom global index. Conclusions: According to the psychological assessment of iatrogenic trigeminal nerve injury patients using SCL-90-R, the patients group, as compared to the control group shows a significantly higher score for somatization, anxiety, and psychoticism. Therefore, assessment of psychological state would be considered to treat patients with iatrogenic trigeminal nerve injury.

• Archives of Craniofacial Surgery
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• v.21 no.4
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• pp.244-248
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• 2020

The infraorbital nerve is a branch of the trigeminal nerve. Injury to the infraorbital nerve can be caused by trauma, including various facial fractures. Due to this nerve injury, patients complain of numbness and pain in the entire cheek, the ala of nose, and upper lip. In general, spontaneous sensory recovery is expected after decompressive surgery. If nerve transection is confirmed, however, neurorrhaphy is typically performed. Here, we present a case in which microsurgery was not performed in a patient with Sunderland grade V avulsion injury of the infraorbital nerve due to a facial bone fracture. Gradual nerve function recovery was confirmed to be possible with conservative treatment and rehabilitation alone. These findings suggest that the nerve function recovery can be expected with conservative treatment, even for severe nerve injury for which microsurgery cannot be considered.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.3
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• pp.331-341
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• 2018

The aim of the present study was to examine the effects of preemptive analgesia on the development of trigeminal neuropathic pain. For this purpose, mechanical allodynia was evaluated in male Sprague-Dawley rats using chronic constriction injury of the infraorbital nerve (CCI-ION) and perineural application of 2% QX-314 to the infraorbital nerve. CCI-ION produced severe mechanical allodynia, which was maintained until postoperative day (POD) 30. An immediate single application of 2% QX-314 to the infraorbital nerve following CCI-ION significantly reduced neuropathic mechanical allodynia. Immediate double application of QX-314 produced a greater attenuation of mechanical allodynia than a single application of QX-314. Immediate double application of 2% QX-314 reduced the CCI-ION-induced upregulation of GFAP and p-p38 expression in the trigeminal ganglion. The upregulated p-p38 expression was co-localized with NeuN, a neuronal cell marker. We also investigated the role of voltage-gated sodium channels (Navs) in the antinociception produced by preemptive application of QX-314 through analysis of the changes in Nav expression in the trigeminal ganglion following CCI-ION. Preemptive application of QX-314 significantly reduced the upregulation of Nav1.3, 1.7, and 1.9 produced by CCI-ION. These results suggest that long-lasting blockade of the transmission of pain signaling inhibits the development of neuropathic pain through the regulation of Nav isoform expression in the trigeminal ganglion. Importantly, these results provide a potential preemptive therapeutic strategy for the treatment of neuropathic pain after nerve injury.

• Journal of Oral Medicine and Pain
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• v.39 no.4
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• pp.133-139
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• 2014

Purpose: There have been reports regarding the various factors associated with the level of discomfort and recovery from neurosensory symptoms in patients with trigeminal nerve injury. However, the contributing factors remain uncertain and poorly understood. The purpose of this paper was to investigate the possible association between various factors expected to affect neurosensory discomfort and recovery in patients with mandibular nerve injury after dental implant surgery. Methods: Eighty-nine post-dental implant surgery patients with mandibular nerve injury were enrolled in this retrospective analysis. A medical records review of the patients was done to determine if the patients' improvement was related to pain intensity, the length of time between the injury and removal of the implant or the depth of penetration of the implant into the mandibular canal as determined by cone-beam computed tomography. Results: There was no significant linear relationship between pain intensity and symptomatic improvement (p=0.319). There was no significant linear relationship between the level of mandibular canal penetration and either pain intensity (p=0.588) or symptomatic improvement (p=0.760). There was a statistically significant linear relationship between length of time before the injury was treated, both with pain intensity (p=0.004), and symptomatic improvement (p=0.024). Conclusions: Our findings indicate that the length of time between nerve injury and initiation of conservative treatment is more closely related to the pain intensity and symptomatic improvement than other factors, including the level of mandibular canal invasion. Additionally, increased pain intensity and decreased symptomatic improvement can be expected over time, because of this linear trend. Therefore, although direct injury to the nerve is the most important factor contributing to a neurosensory disturbances, early neurosensory assessment and initiation of conservative treatment should be done to optimize recovery.

• Journal of Oral Medicine and Pain
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• v.41 no.3
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• pp.118-125
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• 2016

Purpose: The aims of this study were to evaluate the clinical characteristics of patients with altered sensation and/or pain, and to determine outcome predictors affecting persistent neuropathy. Methods: Patients who complained an altered sensation or pain following trigeminal nerve trauma were involved in this study. To determine outcome predictors affecting persistent neuropathy, the patients were divided into two groups; transient vs. persistent, and the clinical phenotypes are compared between groups. Data were analyzed with t-tests, chi-square, and multiple regression analyses with 95% confidence interval and p<0.05 significance level. Results: A total of 111 patients were included: 23 with transient and 88 persistent groups. The panoramic result and pin-prick test score were statistically different between the groups. Radiating symptoms after blunt and pinprick stimuli were also significantly different between groups. The results revealed that the presence of a neurologic lesion in the panoramic view result, reduced sensation in the pinprick test, and radiation in the pinprick test could affect the persistent group. Conclusions: The presence of a neurologic lesion in panoramic view result and reduced sensation and radiating symptoms in the pin prick test would be defining features of one of the main clinical features of persistent neuropathy. These features could serve as outcome predictors diagnosing the permanent nerve injury in trigeminal nerve.

• The Korean Journal of Pain
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• v.35 no.4
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• pp.383-390
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• 2022

Background: The treatment of trigeminal neuralgia remains a challenging issue. Stem cells from human exfoliated deciduous teeth (SHED) provide optimized therapy for chronic pain. This study aimed to investigate the mechanisms underlying the attenuation of trigeminal neuralgia by SHED. Methods: Trigeminal neuralgia was induced by chronic constriction injury of the infraorbital nerve. The mechanical threshold was assessed after model establishment and local SHED transplantation. Endoplasmic reticulum (ER) morphology and Caspase12 expression in trigeminal ganglion (TG) was evaluated as well. BiP expression was observed in PC12 cells induced by tunicamycin. Results: The local transplantation of SHED could relieve trigeminal neuralgia in rats. Further, transmission electron microscopy revealed swelling of the ER in rats with trigeminal neuralgia. Moreover, SHED inhibited the tunicamycin-induced up-regulated expression of BiP mRNA and protein in vitro. Additionally, SHED decreased the up-regulated expression of Caspase12 mRNA and protein in the TG of rats caused by trigeminal neuralgia after chronic constriction injury of the infraorbital nerve mode. Conclusions: This findings demonstrated that SHED could alleviate pain by relieving ER stress which provide potential basic evidence for clinical pain treatment.

• Journal of Korean Dental Science
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• v.5 no.2
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• pp.45-47
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• 2012