• 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.

• The Journal of the Korean dental association
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• v.49 no.6
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• pp.327-333
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• 2011

Clinically, treatment goal of neuropathic pain focused on not elimination of etiology but management and control of symptoms because we don't know certain about clear etiology of neuropathic pain yet. The drugs used for the management of neuropathic pain were classified as drugs with strong evidence for benefit(antidepressants, anticonvulsants, opioid analgesics etc.), modest evidence for benefit(mexiletine, carbamazepine, clonidine etc.), preliminary evidence for benefit(NSAIDs, dextromethorphan, topiramate etc.). Finally, the treatment for trigeminal neuralgia was outlined separately since this disorder responds to a different group of drugs than other neuropathic pain conditions.

• International Journal of Oral Biology
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• v.42 no.3
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• pp.129-135
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• 2017

The present study investigated the role of spinal glutamate recycling in the development of orofacial inflammatory pain or trigeminal neuropathic pain. Experiments were carried out on male Sprague-Dawley rats weighing between 230 and 280 g. Under anesthesia, a polyethylene tube was implanted in the atlanto-occipital membrane for intracisternal administration. IL-$1{\beta}$-induced inflammation was employed as an orofacial acute inflammatory pain model. IL-$1{\beta}$ (10 ng) was injected subcutaneously into one vibrissal pad. We used the trigeminal neuropathic pain animal model produced by chronic constriction injury of the infraorbital nerve. DL-threo-${\beta}$-benzyloxyaspartate (TBOA) or methionine sulfoximine (MSO) was administered intracisternally to block the spinal glutamate transporter and the glutamine synthetase activity in astroglia. Intracisternal administration of TBOA produced mechanical allodynia in naïve rats, but it significantly attenuated mechanical allodynia in rats with interleukin (IL)-$1{\beta}$-induced inflammatory pain or trigeminal neuropathic pain. In contrast, intracisternal injection of MSO produced anti-allodynic effects in rats treated with IL-$1{\beta}$ or with infraorbital nerve injury. Intracisternal administration of MSO did not produce mechanical allodynia in naive rats. These results suggest that blockade of glutamate recycling induced pro-nociception in na?ve rats, but it paradoxically resulted in anti-nociception in rats experiencing inflammatory or neuropathic pain. Moreover, blockade of glutamate reuptake could represent a new therapeutic target for the treatment of chronic pain conditions.

• Journal of Dental Anesthesia and Pain Medicine
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• v.23 no.6
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• pp.357-362
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• 2023

Trigeminal neuralgia (TN) is neuropathic pain that affects the trigeminal nerve branches. Facial pain experienced by patients with TN is typically intense and excruciating. The second and third branches (maxillary and mandibular) are commonly affected. This case report focuses on the potential treatment options for acute TN attacks involving these branches. The proposed approach involves extra-oral peripheral blocks using local anesthetics. Pain levels were measured using a visual numeric scale (VNS) with potential side effects and other relevant documented information. The patients showed responses from high pain levels to almost complete remission (from 8 to 2 and from 10 to 2 on the final VNS), with no significant side effects. This technique provides immediate pain relief and complements oral medications by offering comfort and confidence until the desired drug effect is achieved.

• 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 the Korean Association of Oral and Maxillofacial Surgeons
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• v.33 no.3
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• pp.227-237
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• 2007

Microglial cell activation is known to contribute to neuropathic pain following spinal sensory nerve injuries. In this study, I investigated its mechanisms in the case of trigeminal sensory nerve injuries by which microglial cell and p38 mitogen-activated protein kinase (p38 MAPK) activation in the medullary dorsal horn (MDH) would contribute to the facial pain hypersensitivity following mandibular nerve transection (MNT). And also investigated the changes of trigeminal ganglion neurons and ERK, p38 MAPK manifestations. Activation of microglial cells was monitored at 1, 3, 7, 14, 28 and 60 day using immunohistochemical analyses. Microglial cell activation was primarily observed in the superficial laminae of the MDH. Microglial cell activation was initiated at postoperative 1 day, maximal at 3 day, maintained until 14 day and gradually reduced and returned to the basal level by 60 days after MNT. Pain hypersensitivity was also initiated and attenuated almost in parallel with microglial cell activation pattern. To investigate the contribution of the microglial cell activation to the pain hypersensitivity, minocycline, an inhibitor of microglial cell activation by means of p38 MAPK inhibition, was administered. Minocycline dose-dependently attenuated the development of the pain hypersensitivity in parallel with inhibition of microglial cell and p38 MAPK activation following MNT. Mandibular nerve transection induced the activation of ERK, but did not p38 MAPK in the trigeminal ganglion. These results suggest that microglial cell activation in the MDH and p38 MAPK activation in the hyperactive microglial cells play an important role in the development of facial neuropathic pain following MNT. The results also suggest that ERK activation in the trigeminal ganglion contributes microglial cell activation and facial neuropathic pain.

• The Journal of the Korean dental association
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• v.49 no.6
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• pp.321-326
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• 2011

Neuropathic pain is caused by functional abnonnalities of structural lesions in the peripheral or central nervous system, and occurs without peripheral nociceptor stimulation. Trigeminal neuropathy always pose differential location difficulties as multiple diseases are capablc of producing them: they can be the result of traumatism, tumors, or diseases of the connective tissue, infectious or demyelinating diseases, or may be of idiopathic origin. There are a number of mechanisms described as causing neuropathy. They can be described as ectopic nerve activity, neuroma, ephatic trasmission, change of sodium channel expression, sympathetic activity, central sensitization, and alteration in central inhibition systems. More than I mechanism may be active to create individual clinical presentations. In order to provide better pain control, the mechanism-based approach in treating neuropathic pain should be familiar to physicians.

• International Journal of Oral Biology
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• v.37 no.3
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• pp.121-129
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• 2012

Previous clinical studies have demonstrated that gabapentin, a drug that binds to the voltage-gated calcium channel ${\alpha}2{\delta}1$ subunit proteins, is effective in the management of neuropathic pain, but there is limited evidence that addresses the participation of glial cells in the antiallodynic effects of this drug. The present study investigated the participation of glial cells in the anti-nociceptive effects of gabapentin in rats with trigeminal neuropathic pain produced by mal-positioned dental implants. Under anesthesia, the left mandibular second molar was extracted and replaced by a miniature dental implant to induce injury to the inferior alveolar nerve. Mal-positioned dental implants significantly decreased the air-puff thresholds both ipsilateral and contralateral to the injury site. Gabapentin was administered intracisternally beginning on postoperative day (POD) 1 or on POD 7 for three days. Early or late treatment with 0.3, 3, or 30 ${\mu}g$ of gabapentin produced significant anti-allodynic effect in the rats with mal-positioned dental implants. On POD 9, in the mal-positioned dental implants group, OX-42, a microglia marker, and GFAP, an astrocyte marker, were found to be up-regulated in the medullary dorsal horn, compared with the naive group. However, the intracisternal administration of gabapentin (30 ${\mu}g$) failed to reduce the number of activated microglia or astrocytes in the medullary dorsal horn. These findings suggest that gabapentin produces significant antinociceptive effects, which are not mediated by the inhibition of glial cell function in the medullary dorsal horn, in a rat model of trigeminal neuropathic pain.

• Journal of Dental Anesthesia and Pain Medicine
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• v.20 no.6
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• pp.403-408
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• 2020

Trigeminal neuralgia (TN) involves chronic neuropathic pain, characterized by attacks of repeating short episodes of unilateral shock-like pain, which are abrupt in onset and termination. Anticonvulsants, such as carbamazepine, are the gold standard first-line drugs for pharmacological treatment. Microvascular decompression (MVD) surgery is often the course of action if pharmacological management with anticonvulsants is unsuccessful. MVD surgery is an effective therapy in approximately 83% of cases. However, persistent neuropathic pain after MVD surgery may require reintroduction of pharmacotherapy. This case report presents two patients with persistent pain after MVD requiring reintroduction of pharmacological therapy. Although MVD is successful for patients with failed pharmacological management, it is an invasive procedure and requires hospitalization of the patient. About one-third of patients suffer from recurrent TN after MVD. Often, alternative treatment protocols, including the reintroduction of medications, may be necessary to achieve improvement. This case report presents two cases of post-MVD recurrent pain. Further research is lacking on the success rates of subsequent medication therapy after MVD has proven less effective in managing TN.

• The Journal of the Korean dental association
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• v.45 no.12 s.463
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• pp.728-732
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• 2007