• The Korean Journal of Pain
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• v.21 no.1
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• pp.11-17
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• 2008

Background: Peripheral nerve injury induces up-regulation of the calcium channel alpha2delta (${\alpha}2{\delta}$) subunit and TRPM8 in the dorsal root ganglion (DRG) which might contribute to allodynia development. We investigated the expression of the ${\alpha}2{\delta}$ subunit and TRPM8 in the DRG of sympathetically maintained pain (SMP) and sympathetic independent pain (SIP) rat model. Methods: For the SMP model, the L5 and L6 spinal nerves were ligated tightly distal to the DRG. For the SIP model, the tibial and sural nerves were transected, while the common peroneal nerve was spared. After a 7 day postoperative period, tactile and cold allodynia were assessed using von Frey filaments and acetone drops, respectively. Expression of the ${\alpha}2{\delta}$ subunit and TRPM8 in the L5 and L6 DRG were subsequently examined by a Western blot. Results: There were no significant differences between the two models for the thresholds of tactile and cold allodynia. Expression of the ${\alpha}2{\delta}$ subunit in the ipsilateral DRG to the injury was increased as determined on a Western blot as compared to that in the contralateral or sham-operated DRG of the SMP model, but there was no difference in expression seen with the use of the SIP model. There was no difference in the expression of TRPM8 in the ipsilateral DRG to the injury and the contralateral or sham-operated DRG of either model. Conclusions: Up-regulation of the ${\alpha}2{\delta}$ subunit in injured DRG may play a role that contributes to tactile allodynia development in SMP, but not TRPM8 to cold allodynia after peripheral nerve injury.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.5
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• pp.237-243
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• 2004

Glial cells are activated in neuropathy and play a key role in hyperalgesia and allodynia. This study was performed to determine whether minocycline could attenuate heat hyperalgesia and mechanical allodynia, and how glial cell activation and nuclear factor kappa B (NF-kappaB) were regulated by minocycline in a model of chronic constriction of sciatic nerve (CCl). When minocycline (50 mg/kg, oral) was daily administered from 1 day before to 9 days after ligation, heat hyperalgesia and mechanical allodynia were attenuated. Furthermore, when minocycline treatment was initiated 1 or 3 days after ligation, attenuation of the hypersensitive behavior was still robust. However, the effect of attenuation was less when minocycline was started from day 5. In order to elucidate the mechanism of pain attenuation by minocycline, we examined the changes of glia and NF-kappaB, and found that attenuated hyperalgesia and allodynia by minocycline was accompanied by reduced microglial activation. Furthermore, the number of NF-kappaB immunoreactive cells increased after CCI treatment and this increase was attenuated by minocycline. We also observed translocation of NF-kappaB into the nuclei of activated glial cells. These results suggest that minocycline inhibits activation of glial cells and NF-kappaB, thereby attenuating the development of behavioral hypersensitivity to stimuli.

• The Academic Congress of Korean Shoulder and Elbow Society
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• 2009.03a
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• pp.208-208
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• 2009

Eleven shoulders (9 patients) with refractory scapulothoracic dysfunction were treated with scapulothoracic arthrodesis between 2000 and 2006. Refractory shoulder dysfunction included facioscapulohumeral muscular dystrophy in five shoulders (3 patients), refractory scapular winging with long thoracic nerve palsy in one shoulder, scapular winging caused by serratus anterior palsy with trapezius dysfunction in one shoulder, post-surgical thoracic outlet syndrome due to medial clavicle resection in two shoulders, refractory scapular winging with spinal accessory nerve injury in one shoulder, and chronic trapezius rupture caused by cervical spine surgery in one shoulder. The mean active flexion was improved from 82 degrees preoperatively to 112 degrees postoperatively. The mean Constant score was improved from 27.2 points to 68.0 points. Two shoulders (1 patient) that had facioscapulohumeral muscular dystrophy had broken wires due to nonunion, and one patient had a reactive pulmonary effusion. In ten of the eleven shoulders, the patients were satisfied with their results. The scapulothoracic arthrodesis can cause significant pain relief and functional improvement in refractory scapulothoracic and/or shoulder dysfunction. By selecting patients that present with appropriate indications, and using experienced surgical technique through complete preoperative evaluation, we can diminish the complication rate and make good clinical outcomes.

• The Korean Journal of Pain
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• v.3 no.2
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• pp.165-171
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• 1990

The reflex sympathetic dystrophy syndrome (RSDS) consists of sustained burning pain and tenderness, vasomotor instabilitiy, swelling, occasional functional instability, trophic skin change and edema of extremity following trauma, peripheral nerve injury, spinal cord injury, infection, burn and other etiologic factors. The most important thing in RSDS is to start the treatment as soon as the disease was diagnosed. Most patients with RSDS respond dramatically and permanently to sympathetic blocks if treatment is instituted before irreversible trophic changes. The characteristic radiological finding in RSDS is a patchy osteoporosis in the cancellous bone. Periarticular hyperactivity is seen in RSDS by Tc99m bone scan. We have managed 4 cases of RSDS. The methods of management and effects are as follows: 1) In case 1, 28 lumbar sympathetic blocks in both sides were performed. The patient did not complain of pain or tenderness and the limping improved. 2) In case 2, 7 lumbar sympathetic blocks were performed, but we could find only a slight improvement in the symptoms. 3) In case 3, 8 stellate ganglion blocks were carried out. The patient refused the treatment of RSDS because of the lack of rapid improvement. 4) In case 4, total 64 stellate ganglion blocks were carried out; the patient was permanently improved.

• The Korean Journal of Pain
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• v.22 no.1
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• pp.1-15
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• 2009

Neuropathic pain is often refractory to intervention because of the complex etiology and an incomplete understanding of the mechanisms behind this type of pain. Glial cells, specifically microglia and astrocytes, are powerful modulators of pain and new targets of drug development for neuropathic pain. Glial activation could be the driving force behind chronic pain, maintaining the noxious signal transmission even after the original injury has healed. Glia express chemokine, purinergic, toll-like, glutaminergic and other receptors that enable them to respond to neural signals, and they can modulate neuronal synaptic function and neuronal excitability. Nerve injury upregulates multiple receptors in spinal microglia and astrocytes. Microglia influence neuronal communication by producing inflammatory products at the synapse, as do astrocytes because they completely encapsulate synapses and are in close contact with neuronal somas through gap junctions. Glia are the main source of inflammatory mediators in the central nervous system. New therapeutic strategies for neuropathic pain are emerging such as targeting the glial cells, novel pharmacologic approaches and gene therapy. Drugs targeting microglia and astrocytes, cytokine production, and neural structures including dorsal root ganglion are now under study, as is gene therapy. Isoform-specific inhibition will minimize the side effects produced by blocking all glia with a general inhibitor. Enhancing the anti-inflammatory cytokines could prove more beneficial than administering proinflammatory cytokine antagonists that block glial activation systemically. Research on therapeutic gene transfer to the central nervous system is underway, although obstacles prevent immediate clinical application.

• The Journal of the Korea Contents Association
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• v.10 no.1
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• pp.286-294
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• 2010

Complex Regional Pain Syndrome(CRPS) is a chronic neruopathic pain syndrome, most frequently encountered after trauma, nerve injury, fracture, cerebral vascular accident(CVA), spinal injury, and surgery to a limb, and affected by diverse factors such as disease process, intervention method, and other biopsychosocial components. Occupational therapy as a multidisciplinary treatment approach may be potentially useful when simultaneously targeting such biological, psychological, and social components. Biological treatment can focus on increasing functional use of extremity for promoting independence. Psychological intervention can include relaxation/biofeedback training and cognitive-behavioral treatments, and social approach can focus on recreational therapy and vocational rehabilitation. Occupational therapy will encourage functional restoration, pain management, and regaining of psychological components with collaboration between different disciplines.

• The Korean Journal of Pain
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• v.26 no.4
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• pp.356-360
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• 2013

Background: Nerve injury sometimes leads to chronic neuropathic pain associated with neuroinflammation in the nervous system. In the case of chronic neuropathic pain, the inflammatory and algesic mediators become predominant and result in pain hypersensitivity following nervous system damage. It is well known that urinary trypsin inhibitor (ulinastatin, UTI) has an anti-inflammatory activity. Recently, the neuroprotective action of UTI on the nervous system after ischemic injury has been reported. Thus, we evaluated the neuroprotective effect of ulinastatin in a rat model of neuropathic pain. Methods: Neuropathic pain was induced with L5 spinal nerve ligation (SNL) in male Sprague-Dawley rats weighing 100-120 g. The rats were divided into 3 groups, with n = 8 in each group. The rats in the control group (group 1) were administered normal saline and those in group 2 were administered UTI (50,000 U/kg) intravenously through the tail vein for 3 days from the day of SNL. Rats in group 3 were administered UTI (50,000 U/kg) intravenously from the $5^{th}$ day after SNL. The paw withdrawal threshold was measured using the von Frey test for 3 days starting from the $5^{th}$ day after SNL. Results: The paw withdrawal thresholds were significantly increased in the rats of group 2 compared to the other groups (P < 0.05). Conclusions: Ulinastatin, which was administered for 3 days after SNL, increased the paw withdrawal threshold and it could have a neuroprotective effect in the rat model of neuropathic pain.

• Applied Microscopy
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• v.39 no.3
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• pp.261-266
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• 2009

This study aim to disclose a possible mechanism for the neuronal cell death induced by peripheral nerve injury following a spinal nerve ligation (SNL) as a neuropathic pain model. Male Sprague-Dawley rats (270~290 g) were used for this study. Pain threshold was evaluated for their response to mechanical (von Frey hairs) stimuli 1, 3, and 7 days after a tight ligation of L5 ventral ramus. In control group, the small ganglion cells were strongly stained with routine toluidine blue (TB), whereas the large ganglion cells showed a little bit weak stainity. Each large ganglion cell is surrounded by perineuronal satellite cells. In experimental groups, small ganglion cells showing apparent degenerative changes increased on 1 day, and showed a peak in degenerative cell number at 3 days group, and decreased gradually at 7 days group. We also found a small number of large-sized ganglion cells showing mild degenerative changes. However their satellite cells ware relatively intact with no typical findings throughout this experiment. Under the electron microscope, small ganglion cells showed various stage and typical features of the dark degeneration including mitochondrial swelling.

• Journal of Acupuncture Research
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• v.22 no.6
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• pp.27-36
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• 2005

Introduction : The aim of the study is to investigate the suppressive action of electroacupuncture on cold alloynia development in the rat model of neuopathic pain. Methods : To produce neuropathic pain, the right superior caudal trunk was resected $1{\sim}2\;mm$ between S1 and S2 spinal nerves. The rats were divided into control and four electroacupuncture groups: Two electroacupuncture groups were given 2 Hz or 100 Hz electroacupuncture for 20 minutes everyday after the sacral nerve injury. Other two electroacupuncture groups were given 2 Hz or 100 Hz electroacupuncture for 20 minutes just one session at one hour after the sacral nerve injury. The right point of Joksamni (ST36) was applied for electroacupuncture. The control group was induced neuropathic pain without electroacupuncture. The cold allodynia was assessed by immersing the tail in $4^{\circ}C$ water. The latency to an abrupt tail movement after rat tail immersion was measured with a cut-off time of 15 sec at 4th, 7th and 14th day after the sacral nerve injury. Results : The results were as follows; 1. At 4th experimental day, there were no significant differences between 2 Hz or 100 Hz electroacupuncture groups and the control group. 2. At 7th experimental day, everyday 2 Hz or 100 Hz electroacupuncture groups showed significant differences compared with the control group. But There were no significant differences between 2 Hz and 100 Hz electroacupuncture groups. 3. At 14th experimental day, everyday 2 Hz electroacupuncture group showed significant differences compared with the control group. But everyday 100 Hz electroacupuncture group showed no significant difference compared with the control group and everyday 2 Hz electroacupuncture group. 4. There were no significant differences between the control and 2 Hz or 100 Hz electroacupuncture groups which were done just one session at one hour after the surgery. 5. Everyday 2 Hz electroacupuncture group showed significant differences in the one session of the 100 Hz electroacupuncture group. Conclusion : Everyday 2 Hz electroacupuncture exerts a suppressive action on cold allodynia development in the rat model of neuropathic pain.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.5
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• pp.1285-1290
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• 2007

The present study aims to identify and characterize genes that cause differen genes between non-responders and responders to electroacupuncture (EA) on mechanical allodynia following peripheral nerve injury. Under sodium pentobarbital anesthesia, animals were subjected to unilateral transection of the superior caudal trunk at the level between S1 and S2 spinal nerves. EA stimulation (2Hz, 0.3 ms, 0.2-0.3 mA) was delivered to Zusanli (ST36) for 30 min 2 weeks after the surgery. The degree of mechanical allodynia was assessed quantitatively by touching the tail with von Frey hair (2.0 g) at 10 min intervals. The rats, which showed an EA-induced decrease of response frequencies under 10 %, were classified as non-responders and those displaying an EA-induced decrease of response frequencies 20 % or more were classified as responders. Results from oligonucleotide microarray, to which cDNAs from the spinal dorsal horn (DH) were applied, showed that hemoglobin beta chain complex and chondroitin sulfate proteoglycan-5 decreased and limbic system-associated membrane protein increased in the non-responder group, whereas calcium-independent alpha-Iatrotoxin receptor homolog-3 increased in the responder group. These results suggest that The functional abnormality of molecules regulating cell adhesion, intracellular signal transduction and cell differentiation in the spinal DH may be involved in the anti-allodynic effect of EA.