• The Korean Journal of Pain
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• v.33 no.1
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• pp.13-22
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• 2020

Background: The continuous search for a novel neuropathic pain drug with few or no side effects has been a main focus of researchers for decades. This study investigated the antinociceptive and neuroprotective effects of bromelain in sciatic nerve ligation-induced neuropathic pain in Wistar rats. Methods: Forty-eight Wistar rats randomly divided into eight groups comprised of six animals each were used for this study. Peripheral neuropathy was induced via chronic constriction of the common sciatic nerve. Thermal hyperalgesic and mechanical allodynia were assessed using a hotplate and von Frey filaments, respectively. The functional recovery and structural architecture of the ligated sciatic nerve were evaluated using the sciatic functional index test and a histological examination of the transverse section of the sciatic nerve. The neuroprotective effects of bromelain were investigated in the proximal sciatic nerve tissue after 21 days of treatment. Results: Bromelain significantly (P < 0.05) attenuated both the thermal hyperalgesia and mechanical allodynic indices of neuropathic pain. There were improvements in sciatic function and structural integrity in rats treated with bromelain. These rats showed significant (P < 0.05) increases in sciatic nerve nuclear transcription factors (nuclear factor erythroid-derived-2-related factors-1 [NrF-1] and NrF-2), antioxidant enzymes (superoxide dismutase and glutathione), and reduced membranelipid peroxidation compared with the ligated control group. Conclusions: This study suggest that bromelain mitigated neuropathic pain by enhancing the activities of nuclear transcription factors (NrF-1 and NrF-2) which increases the antioxidant defense system that abolish neuronal stress and structural disorganization.

• Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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• v.12 no.1
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• pp.46-54
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• 2001

Background and Objectives : Nitric oxide(NO) is a short-lived molecule with messenger and cytotoxic functions in nervous, cardiovascular, and immune systems. Among the three distinct NOS isoforms, the neuronal isoform is expressed in small, discrete neuronal populations of CNS and PNS. Axonal injury in adult animals results in a dramatic NOS up-regulation in many types of central and peripheral neurons which normally lack the enzyme or express it only at very low levels. In previous study, we confirmed the efficacy of PEMS on the early functional recovery in rats with surgically transected and reanastomosed recurrent laryngeal nerve. Therefore, after we obtained functionally recovered rats using PEMS in this study, we studied to evaluate the expression of nNOS through the analysis of the difference between functional recovery group and non-recovery group in the recurrent laryngeal nerve. Materials and Method : Using 84 healthy male Sprague-Dawley rats, transections and primary anastomosis were performed on their left recurrent laryngeal nerves. Rats were then randomly assigned to 2 groups. The rats in group A(n=42) received PEMS by placing them in custom cages equipped with Helm-holz coils(3 hr/day, 5 days/wk, for 12 wk). The rats in group B(n=42) were handled the same way as the group A, except that they did not receive PEMS. Laryngovideoendoscopy was performed before and after surgery and followed up weekly. Laryngeal EMG was obtained in both PCA and TA muscles. Immunohistochemisty staining using monoclonal anti-neuronal nitric oxide synthase(nNOS) antibody was performed to detect nNOS in recurrent laryngeal nerve and nodose ganglion. Results : 20 rats(63%) in group A and 5 rats(17%) in the group B showed recovery of vocal fo1d motion. The number of NOS-positive cells was increased in functionally-recovered rats. NOS-staining intensity was reduced 12 weeks after nerve injury. The difference between PEMS group and non-stimulated group was not found. Conclusion : This study shows that nNOS may exert a beneficial effect on nerve regeneration and functional repair.

• The Korean Journal of Pain
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• v.27 no.3
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• pp.239-245
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• 2014

Background: Neuropathic pain induced by spinal or peripheral nerve injury is very resistant to common pain killers, nerve block, and other pain management approaches. Recently, several studies using stem cells suggested a new way to control the neuropatic pain. In this study, we used the spinal nerve L5 ligation (SNL) model to investigate whether intrathecal rat mesenchymal stem cells (rMSCs) were able to decrease pain behavior, as well as the relationship between rMSCs and reactive oxygen species (ROS). Methods: Neuropathic pain of the left hind paw was induced by unilateral SNL in Sprague-Dawley rats (n = 10 in each group). Mechanical sensitivity was assessed using Von Frey filaments at 3, 7, 10, 12, 14, 17, and 24 days post-ligation. rMSCs ($10{\mu}l$, $1{\times}10^5$) or phosphate buffer saline (PBS, $10{\mu}l$) was injected intrathecally at 7 days post-ligation. Dihydroethidium (DHE), an oxidative fluorescent dye, was used to detect ROS at 24 days post-ligation. Results: Tight ligation of the L5 spinal nerve induced allodynia in the left hind paw after 3 days post-ligation. ROS expression was increased significantly (P < 0.05) in spinal dorsal horn of L5. Intrathecal rMSCs significantly (P < 0.01) alleviated the allodynia at 10 days after intrathecal injection (17 days post-ligation). Intrathecal rMSCs administration significantly (P < 0.05) reduced ROS expression in the spinal dorsal horn. Conclusions: These results suggest that rMSCs may modulate neuropathic pain generation through ROS expression after spinal nerve ligation.

• The Journal of Korea CHUNA Manual Medicine
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• v.3 no.1
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• pp.111-123
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• 2002

Objectives : There have been many studies of the effect of Bee Venom therapy about arthritis, but no one study was reported about its whole functional mechanism to musculo-skeletal system. This study was designed to investigate the effect, Indication, and side effect of Bee Venom therapy on musculo-skeletal disease by literature review of articles. Results : The effects of Bee Venom therapy to musculo-skeletal system are divided to Anti_inflammatory effect and Anti-nociceptive effect. Anti_inflammatory effect is achieved through competitive chemotaxis, immuno-regulation, increasing of cortisol secretion by stimulating hypothalamus-pituitary gland-adrenal cortex axis. Anti-nociceptive effect is achieved by Anti-inflammatory mechanism and it works similar to anti-nociceptive effect of the acupuncture acting on central and peripheral nociceptive transduction system. The Bee Venom therapy could cause severe side effect, for example, hypersensitivity and anaphylaxis, injury to central nerve system and cardiovascular system, peripheral blood system, and renal dysfunction. Conclusions : With its Anti-inflammatory and Anti-nociceptive mechanism, Bee Venom therapy is considered that has good effects to autoimmune disease, chronic inflammation of various musculo-skeletal disease and various pain syndrome. But the clinician must be careful for its side effects.

• Journal of Biomedical Engineering Research
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• v.36 no.6
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• pp.296-301
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• 2015

Explant culture condition of dorsal root ganglion have been used to investigate the pathophysiology of peripheral nerve injury, while applying for the various clinical symptom such as trauma, pressure, and stretch. However, explant culture is usually contaminated by mitotic cells, which may observed as a newly divided cells including fibroblast or glia. The mitotic cells could be able to interrupt and change the cell signaling that make it difficult to avoid detrimental effects during the experiments. To eliminate mitotic cells, anti-mitotic reagents like mixture of uridine and 5-fluorodeoxyuridine or cytosine arabinoside were added to the cultures on the following day, but there is no research that investigate viability of anti-mitotic reagent in dorsal root ganglion explant culture. In this study, we investigate inhibition effect of cytosine arabinoside to mitotic cells in dorsal root ganglion explant culture. Also we visualized and analyzed anti-mitotic effect and toxicity of cytosine arabinoside in various concentration condition. This dorsal root ganglion explant culture condition can be applied to research that effect and mechanism of various stimulation and chemical application which affect peripheral nerve regeneration.

• The Journal of Korean Physical Therapy
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• v.15 no.2
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• pp.67-74
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• 2003

Nervous system is clinically important, and involved in most disorders directly or indirectly. It could be injury and be a source of symptoms. Injury of central or peripheral nervous system injury may affect that mechanism and interrupt normal function. An understanding of the concepts of axonal transport is important for physical therapist who treat injury of nerves. Three connective tissue layers are the endoneurium, perineurium, epineurium. Each has its own special structural characteristics and functional properties. The blood supply to the nervous system is well equipped in all dynamic and static postures with intrinsic and extrinsic vasculation. After nerve injury, alternations in the ionic compression or pressures within this environment may interfere with blood flow and, consequently conduction and the flow of axoplasm. The cytoskeleton are not static. On the contrary, elements of the cytoskeleton are dynamically regulated and are very likely in continual motion. It permits neural mobility. There are different axonal transport systems within a single axon, of which two main flows have been identified : First, anterograde transport system, Secondly, retrograde transport system. The nervous system adapts lengthening in two basic ways. The one is that the development of tension or increased pressure within the tissues, increased intradural pressure. The other is movements that are gross movement and movement occurring intraneurally between the connective tissues and the neural tissues. In this article, we emphasize the biologic aspects of nervous system that influenced by therapeutic approaches. Although identified scientific information in basic science is utilized at clinic, we would attain the more therapeutic effects and develop the physical therapy science.

• 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.

• IMMUNE NETWORK
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• v.13 no.6
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• pp.289-294
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• 2013

Lipocalin-2 (LCN2) is an acute-phase protein induced by injury, infection, or other inflammatory stimuli. LCN2 binds small hydrophobic ligands and interacts with cell surface receptor to regulate diverse cellular processes. The role of LCN2 as a chemokine inducer in the central nervous system (CNS) has been previously reported. Based on the previous participation of LCN2 in neuroinflammation, we investigated the role of LCN2 in formalin-induced nociception and pathological pain. Formalin-induced nociceptive behaviors (licking/biting) and spinal microglial activation were significantly reduced in the second or late phase of the formalin test in Lcn2 knockout mice. Likewise, antibody-mediated neutralization of spinal LCN2 attenuated the mechanical hypersensitivity induced by peripheral nerve injury in mice. Taken together, our results suggest that LCN2 can be therapeutically targeted, presumably for both prevention and reversal of acute inflammatory pain as well as pathological pain.

• Journal of Electrodiagnosis and Neuromuscular Diseases
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• v.20 no.2
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• pp.139-143
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• 2018

Rhabdomyolysis is a syndrome caused by injury to skeletal muscles and involves leakage of large quantities of potentially toxic intracellular contents into the plasma. It is known that rhabdomyolysis results in peripheral nerve injury, however, reports of bilateral sciatic neuropathy following rhabdomyolysis are rare. We report a case involving a 42-year-old female patient with no past medical history, who presented with sudden bilateral calf pain, redness, and burning sensation with weakness of both lower extremities after sleeping on an electric heating pad following alcohol drinking. Lower extremity magnetic resonance angiography (MRA) revealed multifocal edema with enhancement of bilateral lower extremity muscles. Clinical and electrodiagnostic tests were consistent with the diagnosis of bilateral sciatic neuropathy following rhabdomyolysis. This is a rare case of bilateral sciatic neuropathy following rhabdomyolysis.

• The Korean Journal of Pain
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• v.27 no.3
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• pp.246-252
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• 2014

Background: Neuropathic pain is generally defined as a chronic pain state resulting from peripheral and/or central nerve injury. There is a lack of effective treatment for neuropathic pain, which may possibly be related to poor understanding of pathological mechanisms at the molecular level. Curcumin, a therapeutic herbal extract, has shown to be effectively capable of reducing chronic pain induced by peripheral administration of inflammatory agents such as formalin. In this study, we aimed to show the effect of curcumin on pain behavior and serum COX-2 level in a Chronic Constriction Injury (CCI) model of neuropathic pain. Methods: Wistar male rats (150-200 g, n = 8) were divided into three groups: CCI vehicle-treated, sham-operated, and CCI drug-treated group. Curcumin (12.5, 25, 50 mg/kg, IP) was injected 24 h before surgery and continued daily for 7 days post-surgery. Behavioral tests were performed once before and following the days 1, 3, 5, 7 after surgery. The serum COX-2 level was measured on day 7 after the surgery. Results: Curcumin (50 mg/kg) decreased mechanical and cold allodynia (P < 0.001) and produced a decline in serum COX-2 level (P < 0.001). Conclusions: A considerable decline in pain behavior and serum COX-2 levels was seen in rat following administration of curcumin in CCI model of neuropathic pain. High concentration of Curcumin was able to reduce the chronic neuropathic pain induced by CCI model and the serum level of COX-2.