• The Korean Journal of Pain
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• v.35 no.3
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• pp.271-279
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• 2022

Background: Inflammation is known to underlie the pathogenesis in neuropathic pain. This study investigated the anti-inflammatory and neuroprotective mechanisms involved in antinociceptive effects of co-administration of acetaminophen and L-carnosine in chronic constriction injury (CCI)-induced peripheral neuropathy in male Wistar rats. Methods: Fifty-six male Wistar rats were randomly divided into seven experimental groups (n = 8) treated with normal saline/acetaminophen/acetaminophen + L-carnosine. CCI was used to induce neuropathic pain in rats. Hyperalgesia and allodynia were assessed using hotplate and von Frey tests, respectively. Investigation of spinal proinflammatory cytokines and antioxidant system were carried out after twenty-one days of treatment. Results: The results showed that the co-administration of acetaminophen and L-carnosine significantly (P < 0.001) increased the paw withdrawal threshold to thermal and mechanical stimuli in ligated rats compared to the ligated naïve group. There was a significant (P < 0.001) decrease in the levels of nuclear factor kappa light chain enhancer B cell inhibitor, calcium ion, interleukin-1-beta, and tumour necrotic factor-alpha in the spinal cord of the group coadministered with acetaminophen and L-carnosine compared to the ligated control group. Co-administration with acetaminophen and L-carnosine increased the antioxidant enzymatic activities and reduced the lipid peroxidation in the spinal cord. Conclusions: Co-administration of acetaminophen and L-carnosine has anti-inflammatory effects as a mechanism that mediate its antinociceptive effects in CCI-induced peripheral neuropathy in Wistar rat.

• The Journal of Korean Medicine
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• v.33 no.3
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• pp.133-146
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• 2012

Background: Most antitumor agents have the side effect of chemotherapy-induced peripheral neuropathy (CIPN). Cancer patients who take antitumor agents suffer from CIPN, but there is no known treatment for it. Unlike the central nerve system, the peripheral nerve can self-repair, and the Schwann cell takes this mechanism. Objectives: In this study, we researched the effect of YideungJetong-Tang (YJT) extract on taxol-induced sciatic nerve damage, through in vitro and in vivo experiments. Also, we studied the effect of YJT extract on neurite recovery and anti-inflammatory effect after compression injury of sciatic nerve in vivo. Methods: Vehicle, taxol and taxol+YJT were respectively applied on sciatic nerve cells of rat in vitro, then the cells were cultured. The sciatic nerve cells and Schwann cells were then observed using Neurofilament 200, Hoechst, ${\beta}$ -tubulin, S-$100{\beta}$, caspase-3 and phospho-Erk1/2. CIPN was induced by taxol into the sciatic nerve of rat in vivo, then YJT extract was taken orally. The axons, Schwann cells and neurites of the DRG sensory nerve were then observed using Neurofilament 200, ${\beta}$-tubulin, Hoechst, S-$100{\beta}$, phospho-Erk1/2 and caspase-3. YJT was taken orally after sciatic nerve compression injury, and the changes in axon of the sciatic nerve, Schwann cells and TNF-${\alpha}$ concentration were observed. Results: The taxol and YJT treated group showed significant effects on Schwann cell recovery, neurite growth and recovery. In vivo, YJT compared with control group showed Schwann cell structural improvement and axons recovering effect after taxol-induced Schwann cell damage. After sciatic nerve compression injury, recovery of distal axon, changes of Schwann cell distribution, and anti-inflammatory response were observed in the YJT. Conclusions: Through this study, we found that after taxol-induced neurite damage of sciatic nerve in vivo and in vitro, YJT had significant effects on sciatic nerve growth and Schwann cell structural improvement. In vivo, YJT improved recovery of distal axons and Schwann cells and had an anti-inflammatory effect.

• Journal of Korean Physical Therapy Science
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• v.8 no.2
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• pp.1033-1038
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• 2001

This studies were to investigate the effects of low power Helium-Neon Infra-Red(He-Ne IR) laser on the changes of the chemical components in serum of the peripheral neuropathy in diabetic rats. The twenty one Spraque-Dawley adult male rats were assigned to the 3 groups: the control group(N=7), the diabetic group(n=7) and the laser group(n=7). The diabetic group was induced with a single intravenous injecion of 50mg/kg body weight streptozotocin dissolved to 0.01mol/L citrate buffer, pH 4.5. The experimental1asser group was irradiated low power He-Ne IR laser for 5 minutes every day during 21 days to the diabetic group. The results were as follows: 1. ALT was increased the laser treatment group than the diabetic group. but that was not significant. 2. AST was significantly increased the laser treatment group than the control group and the diabetic group. 3. LDH was significantly decreased the diabetic group and laser treatment group. 4. ALP was significantly increased the diabetic group and laser treatment group. 5. CHOL was significantly decreased the laser treatment group than the diabetic group. 6. TRIG was significantly increased the laser treatment group than the diabetic group. 7. CPK was significantly increased the laser treatment group than the control group and the diabetic group.

• Journal of environmental and Sanitary engineering
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• v.14 no.1
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• pp.88-96
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• 1999

The effect of acute cadmium-neuropathy on phospholipid metabolism in rat sciatic nerve was investigated. An animal model of cadmium neuropathy was induced by feeding diet containing cadmium to Sprague-Dawley rat for two weeks. Four weeks aged Sprague-Dawley rats were divided into four groups : normal control group, 10ppm-cadmium treated group, 100ppm-cadmium treated group, 1000ppm-cadmium treated group, reference drug, myo-inositol-treated group. All rats were sacrificed at the end of two weeks. The rate of incorporation of 2-[3H]myo-inositol into polyphosphinositide was significantly decreased while the rates of incorporation into phospholipid of titratedserine, ethanolamine and choline were unchanged in sciatic nerve obtained from cadmium-treated rat. Continuously the activities of three enzymes concerned with inositol phospholiped metabolism were measured in homogenates of rat sciatic nerves. Cystidine diglyceride transferase and phophatidylinositol kinase showed significantly decreased activities while phosphatidylinositol-4-phosphate kinase did not show any significant change in activity by cadmium treatment. However these deficits of inositol phospholipid metabolism were ameliorated by myo-inositol administration and these effectiveness were more potent in lower dose cadmiumtreated rats than higher dose cadmium-treated rats. These results suggest that cadmium intoxicated peripheral nerve with perturbation of the ployphosphoinositide metabolism and alteration of the enzyme activity which concerned with myo-inositol metabolism.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.6
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• pp.657-666
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• 2017

Paclitaxel, a chemotherapeutic drug, induces severe peripheral neuropathy. Gabapentin (GBT) is a first line agent used to treat neuropathic pain, and its effect is mediated by spinal noradrenergic and muscarinic cholinergic receptors. Electro-acupuncture (EA) is used for treating various types of pain via its action through spinal opioidergic and noradrenergic receptors. Here, we investigated whether combined treatment of these two agents could exert a synergistic effect on paclitaxel-induced cold and mechanical allodynia, which were assessed by the acetone drop test and von Frey filament assay, respectively. Significant signs of allodynia were observed after four paclitaxel injections (a cumulative dose of 8 mg/kg, i.p.). GBT (3, 30, and 100 mg/kg, i.p.) or EA (ST36, Zusanli) alone produced dose-dependent anti-allodynic effects. The medium and highest doses of GBT (30 and 100 mg/kg) provided a strong analgesic effect, but they induced motor dysfunction in Rota-rod tests. On the contrary, the lowest dose of GBT (3 mg/kg) did not induce motor weakness, but it provided a brief analgesic effect. The combination of the lowest dose of GBT and EA resulted in a greater and longer effect, without inducing motor dysfunction. This effect on mechanical allodynia was blocked by spinal opioidergic (naloxone, $20{\mu}g$), or noradrenergic (idazoxan, $10{\mu}g$) receptor antagonist, whereas on cold allodynia, only opioidergic receptor antagonist blocked the effect. In conclusion, the combination of the lowest dose of GBT and EA has a robust and enduring analgesic action against paclitaxel-induced neuropathic pain, and it should be considered as an alternative treatment method.

• Journal of Acupuncture Research
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• v.30 no.2
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• pp.43-53
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• 2013

Objectives : The purpose of this study is to review of Clinical trials related to the treatment of chemotherapy induced-toxicity by acupuncture therapy. Methods : We searched PubMed by using word of "chemotherapy induced, acupuncture" (Limits : Full text available, 10 years, Clinical trials, Humans, English). We analyzed 15 research paper and examined published journals, years, countries, topic, study design, their results, interventions, participants and instruments of assessment. Results : Eleven journals with fifteen papers were searched. These papers were published in USA, Germany, etc. On the topic of these clinical trials, seven of them were about nausea(vomiting), two about peripheral neuropathy, two about hot flash, two about arthralgia and one about neutropenia, one about fatigue. Six of these studies were single blinded, randomized controlled trial. Twelve studies reported significant effect. The median for number of final participants was 35.5 persons. Assessment for outcomes were versatile questionnaire, nerve conduction studies, WBC, ANC, G-CSF examination, etc. Conclusions : Their median for impact factor was 3.650 and average modified Jadad score of six RCTs was 4.33. In order to provide appropriate evidence regarding the effectiveness of acupuncture in treatment for chemotherapy-induced toxicity, more rigorous and well-designed studies are necessary.

• The Journal of Korean Medicine
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• v.41 no.3
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• pp.247-259
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• 2020

Objectives: This review aims to investigate clinical studies related to bee venom pharmacopuncture for cancer patients and to analyze the research trend for further study. Methods: We searched for clinical studies using bee venom pharmacopuncture therapy on patients with cancer through the electronic databases including Pubmed, Cochrane library, OASIS, KISS, NDSL, and KMBASE. There was no restriction on language and publication date, and after selection/exclusion process, the study design, target disease, intervention details including acupoints, treatment frequency and period, outcomes, study results and adverse events were extracted. Results: Thirteen clinical studies were finally selected. There were a randomized controlled trial RCT about the effect of sweet bee venom pharmacopuncture on cancer-related pain, and three case series about chemotherapy-induced peripheral neuropathy. In case reports, there were nine studies about oligodendroglioma, plexiform neurofibroma, breast cancer, prostate cancer, lung cancer, urachal adenocarcinoma, malignant melanoma, and atypical squamous cells of undetermined significance. The bee venom therapy affected the improvement of outcomes such as symptoms, quality of life, tumor response, and lab findings. Conclusions: The present study found that bee venom therapy is applicable to the treatment of cancer patients, and showed some effect on various symptoms. However, due to insufficient number and quality of studies, well designed and high-quality clinical trials are necessary to confirm the effectiveness and safety of bee venom pharmacopuncture therapy in patients with cancer.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.5
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• pp.565-570
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• 2014

The purpose of this study is to report a clinical case of a patient with CIPN (Chemotherapy Induced Peripheral Neuropathy) successfully treated with Korean medicine interventions including acupuncture, herbal medicine and moxibustion. The patient is a female with CIPN who was diagnosed with ascending colon cancer and suffering from paresthesia of extremities after chemotherapy of platinum compounds. The patient was treated mainly with electroacupuncture (Ex-LE 10), indirect moxibustion and herbal medicine (Ucha-Shinki-hwan granule). The clinical outcomes were measured by NCI CTCAE grade, EORTC QLQ-C30 (CIPN20) scale and patient's assessment of symptoms. In this case, the NCI CTCAE grade was improved from II to I. The scores of global health status and functional scale in QLQ-C30 were increased and symptom scale was decreased. Especially, this case shows a noticeable decrease in sensory scale in QLQ-CIPN20. In patient's general assessment, the scale was changed from 10 to 5. Korean medical interventions including acupuncture, herbal medicine and moxibustion could potentially be an effective treatment for CIPN if further researches are conducted.

• Journal of Ginseng Research
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• v.43 no.1
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• pp.58-67
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• 2019

Background: Diabetic neuropathy is one of the most devastating ailments of the peripheral nervous system. Neuropathic pain develops in ~30% of diabetics. Here, we examined the suppressive effect of GS-KG9 on neuropathic pain induced by streptozotocin (STZ). Methods: Hyperglycemia was induced by intraperitoneal injection of STZ. Rats showing blood glucose level > 250 mg/dL were divided into five groups, and treatment groups received oral saline containing GS-KG9 (50 mg/kg, 150 mg/kg, or 300 mg/kg) twice daily for 4 wk. The effects of GS-KG9 on pain behavior, microglia activation in the lumbar spinal cord and ventral posterolateral (VPL) nucleus of the thalamus, and c-Fos expression in the dorsal horn of the lumbar spinal cord were examined. Results: The development of neuropathic pain began at Day 5 and peaked at Week 4 after STZ injection. Mechanical and thermal pains were both significantly attenuated in GS-KG9-treated groups from 10 d after STZ injection as compared to those in the STZ control. GS-KG9 also repressed microglia activation in L4 dorsal horn and VPL region of the thalamus. In addition, increase in c-Fos-positive cells within L4 dorsal horn lamina I and II of the STZ control group was markedly alleviated by GS-KG9. Conclusion: These results suggest that GS-KG9 effectively relieves STZ-induced neuropathic pain by inhibiting microglial activation in the spinal cord dorsal horn and VPL region of the thalamus.

• The Journal of Korean Medicine
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• v.29 no.4
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• pp.68-82
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• 2008

Objective: The purpose of our study was to show the effects of Hwalhyulmaksung-bang (Huoxiemoxing-fang, HHMSB) treatment on cBSA-induced in MN Mouse Model. Methods: We divided the 20 mice into 4 groups. One group, named NR, was not treated. The second group, named CT, was treated with cBSA (7mg/kg i.p) only. The third group, named HH-250, was treated with cBSA (7mg/kg i.p) and HHMSB extract (250mg/kg, p.o). The fourth group, named HH-500, was treated with cBSA (7mg/kg i.p) and HHMSB extract (500mg/kg, p.o). 4 weeks after cBSA, proteinuria, serum albumin, total cholesterol, serum creatinine, BUN, total cell number of spleen and kidney of all groups were measured. CD3e+/CD19+ and CD4+/CD8 cells ratio of peripheral blood, kidney and spleen of all groups were analyzed. $IL-1{\beta}$ and TNF-$\alpha$, IL-6, IgG, IgM, and IFN-$\gamma$ levels of all groups were gauged. Histological analysis of kidney tissue and immunohistochemical staining (CD4, CD8) of kidney were observed. Results: The level of proteinuria significantly decreased and serum albumin increased in the group treated with cBSA and HHMSB extract compared with the control. Total cholesterol decreased but not significantly. CD3e+/CD19cells ratio of peripheral blood is decreased, but CD4+/CD8cells ratio has no significancy. CD3e+/CD19+ and CD4+/CD8 cells percentage of kidney and spleen has no significancy. Level of $IL-1{\beta}$, IL-6 is significantly decreased, and IFN-$\gamma$ is significantly increased on HHMSB compared with control. Total IgG level significantly decreased on HHMSB compared with the control. Thickness of GBM decreased on histological analysis of kidney. Deposition of CD4 and CD8 decreased on immunohistochemical staining of kidney. Conclusions: We conclude that Hwalhyulmaksung-bang treatment may could be a useful remedy agents for treating Membranous Neuropathy(MN) induced by cationized bovine serum albumin.