• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.585-595
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• 2018

Amitriptyline, a tricyclic antidepressant, is commonly used to treat depression and neuropathic pain, but its mechanism is still unclear. We tested the effect of amitriptyline on 5-hydroxytryptamine 3 ($5-HT_3$) receptor currents and studied its blocking mechanism because the clinical applications of amitriptyline overlapped with $5-HT_3$ receptor therapeutic potentials. Using a whole-cell voltage clamp method, we recorded the currents of the $5-HT_3$ receptor when 5-HT was applied alone or co-applied with amitriptyline in cultured NCB-20 neuroblastoma cells known to express $5-HT_3$ receptors. To elucidate the mechanism of amitriptyline, we simulated the $5-HT_3$ receptor currents using Berkeley $Madonna^{(R)}$ software and calculated the rate constants of the agonist binding and receptor transition steps. The $5-HT_3$ receptor currents were inhibited by amitriptyline in a concentration-dependent, voltage-independent manner, and a competitive mode. Amitriptyline accelerated the desensitization of the $5-HT_3$ receptor. When amitriptyline was applied before 5-HT treatment, the currents rose slowly until the end of 5-HT treatment. When amitriptyline was co-applied with 5-HT, currents rose and decayed rapidly. Peak current amplitudes were decreased in both applications. All macroscopic currents recorded in whole cell voltage clamping experiments were reproduced by simulation and the changes of rate constants by amitriptyline were correlated with macroscopic current recording data. These results suggest that amitriptyline blocks the $5-HT_3$ receptor by close and open state blocking mechanisms, in a competitive manner. We could expand an understanding of pharmacological mechanisms of amitriptyline related to the modulation of a $5-HT_3$ receptor, a potential target of neurologic and psychiatric diseases through this study.

• Archives of Plastic Surgery
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• v.36 no.1
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• pp.84-88
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• 2009

Purpose: Compression of the ulnar nerve in the ulnar tunnel is a relatively uncommon condition. Many authors have described several etiologies of ulnar nerve compression. We experienced two cases of ulnar nerve compression in the ulnar tunnel due to an anomalous pulsatile S - shaped ulnar artery. Methods: Case 1: A 51 - year - old man was referred with numbness and paroxysmal tingling sensation along the volar side of the ring and little fingers of his right hand for 6 months. When exploration, the ulnar artery was pulsatile S - shaped and was impinging on the ulnar nerve. To decompress the ulnar nerve, the tortuous ulnar artery was mobilized and translocated radially onto the adjacent fibrous tissue. Case 2: A 41 - year - old man was referred with tingling sensation on the 4 th, 5 th finger of the right hand for 4 months. Sensory nerve conduction velocities of the ulnar nerve was delayed. Preoperative 3D angio CT scan showed an anomalous S - shaped ulnar artery. Same operation was done. Results: The postoperative course was uneventful. After decompression, paroxysmal tingling sensation decreased to less than 1 minute per episode, occurring 1 - 2 times a day. After 4 months, they had no more episodes of numbness and tingling sensation. Examination demonstrated good sensation to pinprick and touch on the ulnar aspect of the hand. Conclusion: We report two cases of ulnar nerve compressive neuropathy that was caused by an anomalous pulsatile S - shaped ulnar artery in the ulnar tunnel. Although this is an unusual cause of ulnar nerve compression, the symptoms will not spontaneously resolve. The prompt relief of compressive neuropathic symptoms following the translocation of the impinging ulnar artery from the affected ulnar nerve onto adjacent tissue proved that the ulnar nerve compression is due to the anomalous vessel.

• The Journal of Korean Physical Therapy
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• v.22 no.1
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• pp.67-73
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• 2010

Purpose: We tested whether repetitive transcranial magnetic stimulation (rTMS) improved recovery following spinal cord injury (SCI) in rats with transplantation of adipose tissue-derived stromal cells (ATSCs). Methods: Twenty Sprague-Dawley rats (200-250 g, female) were used. Moderate spinal cord injury was induced at the T9 level by a New York University (NYU) impactor. The rat ATSCs (approximately $5{\times}10^5$ cells) were injected into the perilesional area at 9 days after SCI. Starting four days after transplantation, rTMS (25 Hz, 0.1 Tesla, pulse width=$370{\mu}s$, on/off time=3 sec/3 sec) was applied daily for 7 weeks. Functional recovery was assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale as well as pain responses for thermal and cold stimuli. Results: Both groups showed similar, gradual improvement of locomotor function. rTMS stimulation decreased thermal and cold hyperalgesia after 7 weeks, but sham stimulation did not. Conclusion: rTMS after transplantation of ATSCs in an SCI model may reduce thermal hyperalgesia and cold allodynia, and may be an adjuvant therapeutic tool for pain control after stem cell therapy in SCI.

• The Korean Journal of Pain
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• v.28 no.1
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• pp.4-10
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• 2015

Etifoxine (etafenoxine, $Stresam^{(R)}$) is a non-benzodiazepine anxiolytic with an anticonvulsant effect. It was developed in the 1960s for anxiety disorders and is currently being studied for its ability to promote peripheral nerve healing and to treat chemotherapy-induced pain. In addition to being mediated by $GABA_A{\alpha}2$ receptors like benzodiazepines, etifoxine appears to produce anxiolytic effects directly by binding to ${\beta}2$ or ${\beta}3$ subunits of the $GABA_A$ receptor complex. It also modulates $GABA_A$ receptors indirectly via stimulation of neurosteroid production after etifoxine binds to the 18 kDa translocator protein (TSPO) of the outer mitochondrial membrane in the central and peripheral nervous systems, previously known as the peripheral benzodiazepine receptor (PBR). Therefore, the effects of etifoxine are not completely reversed by the benzodiazepine antagonist flumazenil. Etifoxine is used for various emotional and bodily reactions followed by anxiety. It is contraindicated in situations such as shock, severely impaired liver or kidney function, and severe respiratory failure. The average dosage is 150 mg per day for no more than 12 weeks. The most common adverse effect is drowsiness at the initial stage. It does not usually cause any withdrawal syndromes. In conclusion, etifoxine shows less adverse effects of anterograde amnesia, sedation, impaired psychomotor performance, and withdrawal syndromes than those of benzodiazepines. It potentiates $GABA_A$ receptor-function by a direct allosteric effect and by an indirect mechanism involving the activation of TSPO. It seems promising that non-benzodiazepine anxiolytics including etifoxine will replenish shortcomings of benzodiazepines and selective serotonin reuptake inhibitors according to animated studies related to TSPO.

• Journal of Hospice and Palliative Care
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• v.12 no.2
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• pp.88-94
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• 2009

Chest pain is a symptom observed commonly in outpatients and emergency room patients, and its causes are variable. Because treatment and prognosis of chest pain are different depending on its cause, it is more important than anything else to accurately diagnose the cause of chest pain. Most of patients complaining of chest pain undergo basic tests at a private local clinic or at the Internal medicine or chest surgery department of a general hospital and, they are referred to the pain clinic, with a note stating no particular finding. However, if they have sustained severe neuropathic pain in spite of nerve block, accurate diagnosis for chest pain is essential. We experienced rapidly developing spine breakdown and cord compression caused by metastatic spinal tumor in an inpatient who was being treated for chest pain, and thus, we report here in the case with literature review.

• The Korean Journal of Pain
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• v.27 no.3
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• pp.219-228
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• 2014

Background: A lipo-prostaglandin E1 agonist is effective for the treatment of neurological symptoms of spinal stenosis when administered by an oral or intravenous route. we would like to reveal the therapeutic effect of an epidural injection of lipo-prostaglandin E1 on hyperalgesia in foraminal stenosis. Methods: A total of 40 male Sprague-Dawley rats were included. A small stainless steel rod was inserted into the L5/L6 intervertebral foramen to produce intervertebral foraminal stenosis and chronic compression of the dorsal root ganglia (DRG). The rats were divided into three groups: epidural PGE1 (EP) (n = 15), saline (n = 15), and control (n = 10). In the EP group, $0.15{\mu}g{\cdot}kg-1$ of a lipo-PGE1 agonist was injected daily via an epidural catheter for 10 days from postoperative day 3. In the saline group, saline was injected. Behavioral tests for mechanical hyperalgesia were performed for 3 weeks. Then, the target DRG was analyzed for the degree of chromatolysis, chronic inflammation, and fibrosis in light microscopic images. Results: From the fifth day after lipo-PGE1 agonist injection, the EP group showed significant recovery from mechanical hyperalgesia, which was maintained for 3 weeks (P < 0.05). Microscopic analysis showed much less chromatolysis in the EP group than in the saline or control groups. Conclusions: An epidurally administered lipo-PGE1 agonist relieved neuropathic pain, such as mechanical hyperalgesia, in a rat foraminal stenosis model, with decreasing chromatolysis in target DRG. We suggest that epidurally administered lipo-PGE1 may be a useful therapeutic candidate for patients with spinal stenosis.

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

• Journal of Medicine and Life Science
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• v.16 no.3
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• pp.96-100
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• 2019

Postural tachycardia syndrome (POTS) is common, although not so well-known variant of cardiovascular autonomic disorder characterized by an excessive heart rate increase on standing. POTS is probably underdiagnosed due to the heterogeneity in both presentation and etiology. This study aimed to evaluate the clinical and autonomic features in patients with POTS. We reviewed the medical records of patients with POTS. Medical records include onset age, sex, presenting symptoms, body mass index (BMI) and prognosis. All patients had an autonomic function and laboratory tests. Ninety-nine patients met the inclusion criteria for POTS (51.5% male; mean±SD age, 20.0±9.7 years; mean±SD, BMI 21.9±3.9). Common presenting symptoms were a brief loss of consciousness, dizziness, blurred vision and headache. Autonomic function tests showed abnormal quantitative sudomotor axon reflex testing in 20 patients of 99 POTS patients. The abnormal post-ganglionic sympathetic sudomotor function is generally considered to reflect a neuropathic form of POTS. In treatments, 83 patients were treated by non-pharmacological management including lifestyle changes and 16 patients required the initiation of pharmacological therapies. Most patients with POTS showed a relatively favorable prognosis. POTS is a chronic disease with a substantial subset of patients recovering within a few years after the initial presentation. Future efforts should focus on better understanding of POTS pathophysiology and designing randomized controlled trials for the selection of more effective therapy.

• YAKHAK HOEJI
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• v.53 no.4
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• pp.217-221
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• 2009

Diabetes mellitus is a group of metabolic disorders characterized by hyperglycemia and abnormalities in carbohydrate, fat, and protein metabolism which is resulting chronic microvascular, macrovascular, and neuropathic complications. Therefore, correct and consistent educations for pharmacotherapy is important and especially drug consultation by the specialty pharmacist of diabetic pharmacotherapy is necessary for all diabetic patients. The purpose of this study is to evaluate the necessity of the specialty pharmacist of diabetic pharmacotherapy and this study was performed from June 31th, 2008 to October 9th, 2008 in Kangnam St. Mary's Hospital, Seoul, S. Korea throughout the questionnaire and evaluated the total 68 patients who were participating the multidisciplinary diabetes team programs. We evaluated the patient characteristics (n=68), learning status (difficulty 70.4%), wanted further education (68.3%) and preference of educator (pharmacist 46%) after finishing team teaching by multidisciplinary diabetes team program. In conclusion, many diabetic patients(80.3%) wanted individual and further drug consultation by the pharmacists who are specialized in the diabetes individually and they are needed.

• Annals of Clinical Neurophysiology
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• v.16 no.1
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• pp.8-14
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• 2014

Background: Early detection of neuropathy may prevent further progression of this complication in the diabetic patients. The purpose of this study was to evaluate the prevalence of early neuropathic complication in patients with newly diagnosed type 1 and type 2 diabetes. Methods: Nerve conduction studies (median, ulnar, posterior tibial, peroneal, and sural nerves) were performed for 49 type 1 (27 males, mean $14.1{\pm}7.5$ years) and 40 type 2 (27 males, $42.0{\pm}14.1$ years) diabetic patients at onset of diabetes. Children with age at onset under 4 years and adults over 55 years were excluded to eliminate the aging effect and the influence of obstructive arteriosclerosis. Neuropathy was defined as abnormal nerve conduction findings in two or more nerves including the sural nerve. Results: Mean HbA1c level was $12.6{\pm}3.3%$ for type 1 and $10.5{\pm}2.9%$ for type 2 diabetes. The prevalence of neuropathy was 12.2% for type 1, and 35.0% for type 2 diabetes, respectively. There were significant trends in the prevalence of neuropathy with increasing age (p<0.05). The effect of the mean level of glycosylated hemoglobin on the prevalence of polyneuropathy at onset of diabetes was borderline (p=0.0532). Neither sex of the patients nor the type of diabetes affected the neurophysiologic abnormalities at the diagnosis. Conclusions: Even in a population with diabetes at the diagnosis, the prevalence of subclinical neuropathy was not low. Neuropathy has been significantly associated with increasing age indicating the possibility of longer duration of undetected diabetes among them, especially in type 2 diabetes.