• International Journal of Oral Biology
• /
• v.34 no.3
• /
• pp.157-164
• /
• 2009

We recently described a novel animal model of trigeminal neuropathic pain following compression of the trigeminal ganglion (Ahn et al., 2009). In our present study, we adapted this model using male Sprague-Dawley rats weighing between 250-260 g and then analyzed the behavioral responses of these animals following modified chronic compression of the trigeminal ganglion. Under anesthesia, the rats were mounted onto a stereotaxic frame and a 4% agar solution ($10{\mu}L$) was injected in each case on the dorsal surface of the trigeminal ganglion to achieve compression without causing injury. In the control group, the rats received a sham operation without agar injection. Air-puff, acetone, and heat tests were performed at 3 days before and at 3, 7, 10, 14, 17, 21, 24, 30, 40, 55, and 70 days after surgery. Compression of the trigeminal ganglion produced nociceptive behavior in the trigeminal territory. Mechanical allodynia was established within 3 days and recovered to preoperative levels at approximately 60 days following compression. Mechanical hyperalgesia was also observed at 7 days after compression and persisted until the postoperative day 40. Cold hypersensitivity was established within 3 days after compression and lasted beyond postoperative day 55. In contrast, compression of the trigeminal ganglion did not produce any significant thermal hypersensitivity when compared with the sham operated group. These findings suggest that compression of the trigeminal ganglion without any injury produces prolonged nociceptive behavior and that our rat model is a useful system for further analysis of trigeminal neuralgia.

• Proceedings of the Korean Biophysical Society Conference
• /
• 2003.06a
• /
• pp.55-55
• /
• 2003

P2X$_3$ receptor, a member of P2 purine receptors, is a ligand-gated ion channel activated by extracellular ATP as an endogenous ligand, and highly localized in peripheral and central sensory neurons. The activation of P2X3 receptor by ATP as the pronociceptive effect has been known to initiate the pain signaling involved in chronic inflammatory nociception and neuropathic pain by nerve injury, implicating the possibility of new drug development to control pains. In this study, we have developed a two electrode voltage clamp (TEVC) assay system to evaluate the inhibitory activity of several newly synthesized PPADS and a novel non-ionic antagonist against ATP activation of human P2X3 receptor. PPADS derivatives include several pyridoxine and pyridoxic acid analogs to study the effects of phosphate and aldehyde functional groups in PPADS. All new PPADS analogs were less potent than PPADS at human P2X$_3$ receptors, however, LDD130, a non-ionic analog showed potent antagonistic property with $IC_{50}$/ of 8.34 pM. In order to uncover the structure activity relationships of LDD130, and design new structural analogs, we synthesized and investigated a few structural variants of LDD130, and the results will be discussed in this presentation.

• Clinical Pain
• /
• v.19 no.2
• /
• pp.90-96
• /
• 2020

Objective: To investigate the diagnostic accuracy of two physical examinations (straight leg raise [SLR] and Bragard test) and electromyography (EMG) in patients with lumbosacral monoradiculopathy in acute and chronic state on confirmation of different diagnostic criteria (MRI vs MRI and diagnostic selective nerve root block [DSNRB]). Method: We identified 297 participants retrospectively from the departmental database. MRI evidence of L5 or S1 nerve root compression and a positive result in diagnostic SNRB served as reference standards. They were divided into two groups by the symptom duration: lasting more than 12 weeks in the chronic group and less than 12 weeks in the acute group. The diagnostic value of clinical tests and EMG were compared. Results: The clinical tests (SLR and Bragard test) done in acute stage on detection by MRI and DSNRB had the highest sensitivity (68%) compared to the chronic stage (63%), but sensitivity was low (57%) on confirmation of MRI alone. However, there was no significant difference on sensitivity and specificity of EMG regardless of reference standards and symptom duration. Electromyography was a significant predictor of neuropathic abnormalities on both acute (OR, 6.3; 95% CI, 2.4 to 16.7; p<0.01) and chronic (OR, 6.8; 95% CI, 2.9 to 16.3; p<0.01). Conclusion: In general, individual physical tests are easy to do and a combination of those tests could be a sensitive indicator of L5 or S1 radiculopathy. Furthermore, the use of provocation tests could provide useful information, especially in proceeding therapeutic selective nerve root block.

• Journal of the Korean Arthroscopy Society
• /
• v.2 no.2
• /
• pp.185-188
• /
• 1998

Spontaneous osteonecrosis of the knee was first described by Ahlbck et al in 1968 as the spontaneous and sudden onset of severe pain, usually on the medial side of the knee joint, in old age(>60 years) with no specific etiologic factors. They differentiate the disease from osteochondritis dissecans, osteoarthritis, fracture, infection, neuropathic joint and secondary osteonecrosis of the knee joint. So far many investigators described this disease but had never observed cases developed in young patient with familial occurrence. The report presented here is a case of spontaneous osteonecrosis of both medial and lateral femoral condyles involving the bilateral knee joint that were treated by arthorscopic loose body removal and multiple drilling.

• Journal of Korean Foot and Ankle Society
• /
• v.18 no.1
• /
• pp.1-7
• /
• 2014

In patients with diabetic foot, ulceration and amputation are the most serious consequences and can lead to morbidity and disability. Peripheral arterial sclerosis, peripheral neuropathy, and foot deformities are major causes of foot problems. Foot deformities, following autonomic and motor neuropathy, lead to development of over-pressured focal lesions causing the diabetic foot to be easily injured within the shoe while walking. Wound healing in these patients can be difficult due to impaired phagocytic activity, malnutrition, and ischemia. Correction of deformity or shoe modification to relieve the pressure of over-pressured points is necessary for ulcer management. Application of selective dressings that allow a moist environment following complete debridement of the necrotic tissue is mandatory. In the case of a large soft tissue defect, performance of a wound coverage procedure by either a distant flap operation or a skin graft is necessary. Patients with a Charcot joint should be stabilized and consolidated into a plantigrade foot. The bony prominence of a Charcot foot can be corrected by a bumpectomy in order to prevent ulceration. The most effective management of the diabetic foot is ulcer prevention: controlling blood sugar levels and neuropathic pain, smoking cessation, stretching exercises, frequent examination of the foot, and appropriate education regarding footwear.

• Mass Spectrometry Letters
• /
• v.6 no.3
• /
• pp.65-70
• /
• 2015

N-Alkyl/benzyl substituted isatin derivatives are intermediates and synthetic precursors for the preparation of biological active heterocycles. N-alkyl/benzyl isatins have showed various biological activities, such as cytotoxicity, antiviral, caspase inhibition, cannabinoid receptor 2 agonists for the treatment of neuropathic pain, etc. In this study, N-alkyl/benzyl isatin derivatives were synthesized from isatin and alkyl/benzyl halides in presence of K₂CO₃ in DMF and excellent to quantitative yields (~95%) were obtained. Isatins and benzyl-isatins were condensed with fluorescein hydrazide to form fluorescein hydrazone. All the compounds were subjected to their fragmentation behavior study using LC/MSⁿ. N-Alkyl substituted isatin derivatives fragmented at nitrogen-carbon (N-C) bond, hence gave daughter ion as [RN+H]⁺. Whereas, N-benzyl substituted isatin derivatives fragmented at carbon-carbon (C-C) bond of alkyl chain which linked with nitrogen molecules, therefore gave N-methyl fragments [RNCH₂]⁺. This study demonstrated that, isatin moiety present in a small/large molecule or in a matrix of reaction mixture with/without N-alkyl/benzyl substituents can be identified by mass spectroscopic fragmentation behavior study.

• Journal of Korean Foot and Ankle Society
• /
• v.17 no.4
• /
• pp.243-250
• /
• 2013

Diabetic Charcot arthropathy is a severe joint disease in the foot and ankle that can result in fracture, permanent deformity, limb loss. Although recent research has improved our level of knowledge regarding its etiology and treatment, it still remains a poorly understood disease. It is a serious and potentially limb-threatening lower-extremity late complication of diabetes mellitus and its diagnosis is commonly missed upon initial presentation. Clinicians treating diabetic patients should be vigilant in recognizing early signs of acute Charcot arthropathy, such as pain, warmth, edema, or pathologic fracture in a neuropathic foot. Early detection and prompt treatment can prevent joint and bone destruction. If left untreated, it can reduce overall quality of life and dramatically increase morbidity and mortality of patients. The goal of this manuscript is to evaluate the current concepts of Charcot arthropathy through review of various literature and help clinicians decide the treatment strategy.

• Biomolecules & Therapeutics
• /
• v.25 no.2
• /
• pp.158-164
• /
• 2017

Methylglyoxal (MGO) is a highly reactive metabolite of glucose which is known to cause damage and induce apoptosis in endothelial cells. Endothelial cell damage is implicated in the progression of diabetes-associated complications and atherosclerosis. Hypericin, a naphthodianthrone isolated from Hypericum perforatum L. (St. John's Wort), is a potent and selective inhibitor of protein kinase C and is reported to reduce neuropathic pain. In this work, we investigated the protective effect of hypericin on MGO-induced apoptosis in human umbilical vein endothelial cells (HUVECs). Hypericin showed significant anti-apoptotic activity in MGO-treated HUVECs. Pretreatment with hypericin significantly inhibited MGO-induced changes in cell morphology, cell death, and production of intracellular reactive oxygen species. Hypericin prevented MGO-induced apoptosis in HUVECs by increasing Bcl-2 expression and decreasing Bax expression. MGO was found to activate mitogen-activated protein kinases (MAPKs). Pretreatment with hypericin strongly inhibited the activation of MAPKs, including P38, JNK, and ERK1/2. Interestingly, hypericin also inhibited the formation of AGEs. These findings suggest that hypericin may be an effective regulator of MGO-induced apoptosis. In conclusion, hypericin downregulated the formation of AGEs and ameliorated MGO-induced dysfunction in human endothelial cells.

• Journal of Korean Medical Science
• /
• v.33 no.44
• /
• pp.279.1-279.16
• /
• 2018

Magnetic resonance-guided focused ultrasound (MRgFUS) is a new emerging neurosurgical procedure applied in a wide range of clinical fields. It can generate high-intensity energy at the focal zone in deep body areas without requiring incision of soft tissues. Although the effectiveness of the focused ultrasound technique had not been recognized because of the skull being a main barrier in the transmission of acoustic energy, the development of hemispheric distribution of ultrasound transducer phased arrays has solved this issue and enabled the performance of true transcranial procedures. Advanced imaging technologies such as magnetic resonance thermometry could enhance the safety of MRgFUS. The current clinical applications of MRgFUS in neurosurgery involve stereotactic ablative treatments for patients with essential tremor, Parkinson's disease, obsessive-compulsive disorder, major depressive disorder, or neuropathic pain. Other potential treatment candidates being examined in ongoing clinical trials include brain tumors, Alzheimer's disease, and epilepsy, based on MRgFUS abilities of thermal ablation and opening the blood-brain barrier. With the development of ultrasound technology to overcome the limitations, MRgFUS is gradually expanding the therapeutic field for intractable neurological disorders and serving as a trail for a promising future in noninvasive and safe neurosurgical care.

• The Journal of Internal Korean Medicine
• /
• v.43 no.3
• /
• pp.451-459
• /
• 2022

Objective: The purpose of this study was to report the effectiveness of modified Guibi-tang in a patient suffering from chemotherapy-induced peripheral neuropathy (CIPN). Methods: A 54-year-old Korean female patient diagnosed with recurrent ovarian cancer had CIPN with other symptoms, such as anorexia, dyspepsia, insomnia, etc. She was diagnosed with Simbiyangheo and hence treated with a modified Guibi-tang. Neuropathic symptoms were assessed using a numerical rating scale (NRS) and a sensory score. Quality of life was assessed using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group Neurotoxicity (FACT/GOG-Ntx). Results: After 14 days of treatment, the patients showed a decrease in NRS for bilateral limb pain and improvement in other symptoms, such as general weakness, insomnia, dizziness, and headache. Quality of life also increased. Conclusion: Modified Guibi-tang may be considered an optional treatment for CIPN if the patient is diagnosed with Simbiyangheo. Further studies are needed to confirm this finding.