• Journal of Acupuncture Research
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• v.20 no.3
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• pp.15-23
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• 2003

Objective : The role of high frequency 120 Hz electroacupuncture(EA) in carrageenan-induced pain was studied by examining the alnalgesic effects, and prostaglandin $E_2(PGE_2)$ levels measurement and spinal N-methyl-D-aspartate(NMDA) receptor expression. Inflammation was induced by an intraplantar injection of 1% carrageenan into the right hind paw. Method : Bilateral EA stimulation with 120 Hz were delivered at those acupoints corresponding to Zusanli and Sanyinjiao in man via the needles for a total of 30 min duration in carrageenan-injected rats. Results : EA stimulation showed significant analgesic effects as measured by analgesy-meter at all time points tested compared with controls. Three hours after carrageenan injection, PGE2 levels were measured by commercial kit. EA significantly inhibited PGE2 production in the right paw. The number of NR1 and NR2A, NMDA receptor, immunoreactive neurons was significantly increased in the superficial dorsal horn(laminae I-II) and nucleus proprius(laminae III-IV) of ipsilateral spinal cord at L4-5. But the number of carrageenan-induced NR1 and NR2A immunoreactive neuron, especially NR1 immunoreaction in the superficial dorsal horn, was reduced by 120 Hz EA stimulation. Conclusions : These results indicate that NMDA receptors may mediate transmission of nociceptive information originating in tissue inflammation of hind paw and high frequency 120 Hz EA stimulation have an alleviating action against local inflammatory pain.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.1
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• pp.35-45
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• 1999

Excitatory amino acid (EAA) and substance P (SP) have been known to be primary candidates for nociceptive neurotransmitter in the spinal cord, and calcium ions are implicated in processing of the sensory informations mediated by EAA and SP in the spinal cord. In this study, we examined how $Ca^{2+}$ modified the responses of dorsal horn neurons to single or combined iontophoretical application of EAA and SP in the rat. All the LT cells tested responded to kainate, whereas about 55% of low threshold (LT) cells responded to iontophoretically applied NMDA. NMDA and kainate excited almost all wide dynamic range (WDR) cells. These NMDA- and kainate-induced WDR cell responses were augmented by iontophoretically applied EGTA, but suppressed by $Ca^{2+},\;Mn^{2+},$ verapamil and ${\omega}-conotoxin$ EVTA, effect of verapamil being more prominent and well sustained. $Ca^{2+}$ and $Mn^{2+}$ antagonized the augmenting effect of EGTA. On the other hand, prolonged spinal application of EGTA suppressed the response of WDR cell to NMDA. SP had triple effects on the spontaneous activity as well as NMDA-induced responses of WDR cells: excitation, inhibition and no change. EGTA augmented, but $Ca^{2+},\;Mn^{2+}$ and verapamil suppressed the increase in the NMDA-induced responses and spontaneous activities of WDR cells following iontophoretical application of SP. These results suggest that in the spinal cord, sensory informations mediated by single or combined action of EAA and SP can be modified by the change in calcium ion concentration.

• Journal of Sasang Constitutional Medicine
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• v.13 no.1
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• pp.88-96
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• 2001

To evaluate the effect of Yuldahansotang(YHT) water extract on cultuted mouse spinal sensory neuron which was inhibited by xanthine oxidase(XO) and hypoxanthine(HX)-induced oxigen radicals, MIT assay, NR assay, Neurofilament enzymeimmuno assay and LDH activity assay were carried our after the cultured mouse spinal sensory neuron were preincubated with various concentrations of YHT water extract for 3 hours prior to exposure of XO/HX. The results obtained were as follows: 1. XO/HX, a oxigen radical, decreased the survival rate of the cultured mouse spinal sensory neuron cells on NR assay and MTT assay. 2. MTT50 value and NR50 value pf XO/HX were 20 mU/ml XO/0.2 mM HX and 40 mU/ml XO/0.2 mM HX. 3. YHT water extract have efficacy of increasing neurofilament. 4. YHT water extract have efficacy of increasing LDH activity. From above the results, It is concluded that YHT has marked efficacy as a treatment for the damages caused in the XO/HX-mediated oxidative process.

• Korean Journal of Acupuncture
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• v.23 no.3
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• pp.55-71
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• 2006

Objectives : The present study was investigated the effect and pathway of heterotopic electroacupuncture (EA) on pain induced by formalin in rats. Methods : Acupoints in the right forepaws, $HT_7$ and $PC_7$, were stimulated with 3 mA, 2 ms, and 10 Hz before subcutaneously formalin injection (5%, $50{\mu}l$) to the left hind paw. Moreover, it was investigated whether the dorsolateral funiculus (DLF), as known to the descending inhibition, mediates analgesia of the heterotopic EA, and an administration of naltrexone blocks the effect of EA. Results : In the immunohistochemistry of cFos-like protein (cFL), there were inhibitory effects of EA on the increased expression of cFL in the lumbar spinal dorsal horn neurons following formalin injection. Especially, EA inhibited the expression of cFL on the superficial laminae than that on the deep laminae at 1 hr after, but that on the deep laminae than that on the superficial laminae at 2 hr after. Also, EA suppressed the increased expression of nitric oxide (NO) and neuronal nitric oxide synthase (nNOS) in the lumbosacral spinal cord after formalin injection, but not Sham-EA. Suppressed expressions of cFL, NO and nNOS in the spinal cord were eliminated after transection of the ipsilateral DLF at $T_{10}{\sim}T_{11}$ levels. However, pretreatment of naltrexone could not prevent the suppressive expressions of cFL, NO and nNOS at the spinal cord. Conclusions : These results suggest that the analgesia of heterotopic EA may be modulated through the DLF constituting the descending inhibition.

• Journal of the Korean Society of Physical Medicine
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• v.9 no.2
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• pp.193-200
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• 2014

PURPOSE: This study examined the effects of treadmill exercise of diverse intensities on the expression of IL-$1{\beta}$ (interleukine-$1{\beta}$) in the spinal cord in osteoarthritis rats. METHODS: The authors applied treadmill exercise of diverse intensity for 4 weeks to Sprague-Dawley rats to which intra-articular injection of monosodium iodoacetate(MIA, $3mg/50{\mu}l$, diluted in saline) was applied in the right knee joint to induce osteoarthritis. The four-week exercise was not applied to the control group(CG, n=15), while exercise of applicable intensity was applied to the low-intensity exercise group(LEG, n=15), moderate-intensity exercise group (MEG, n=15), and high-intensity exercise group(HEG, n=15) for four weeks. Observations were made of expression of IL-$1{\beta}$ in the spinal cord in osteoarthritis rats using western blot analysis. RESULTS: There were significant differences(p<.05) in the comparison of expression of IL-$1{\beta}$ in the spinal cord between the four groups involved. And the LEG and MEG had reduced expression of IL-$1{\beta}$ significantly than the CG(p<.05); in particular, the MEG showed the lowest expression. On the other hand, the HEG had more elevated expression of IL-$1{\beta}$ significantly than the CG(p<.05). CONCLUSION: As a result, factors that induce neuropathic pain such as IL-$1{\beta}$ are reduced; thus, the recovery of damaged neurons is improved and neuropathic pain is reduced. Further, when prescribing exercise to treat osteoarthritis patients, exercise of moderate intensity suitable for patients' physical conditions, rather than high intensity, maximizes the effects of this therapy.

• The Korean Journal of Pain
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• v.13 no.2
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• pp.164-174
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• 2000

Background: After an injury to tissue such as the skin, hyperalgesia develops. Hyperalgesia is characterized by an increase in the magnitude of pain evoked by noxious stimuli. It has been postulated that in the mechanism of hyperalgesia (especially secondary hyperalgesia) and allodynia, a sensitization of central nervous system such as spinal dorsal horn may contribute to development of hyperalgesia. However, the precise mechanism is still unclear. In the present study, we investigated the roles of N-methyl-D-aspartate (NMDA) receptor and nitric oxide (NO) system in the mechanism of hyperalgesia, and their relations with c-fos expression Methods: Inflammation was induced by injection of complete Freund adjuvant (CFA) into unilateral hindpaw of Sprague-Dawley rat. Behavioral studies measuring paw withdrawal responses by von Frey filaments and paw withdrawal latencies by radiant heat stimuli and stainings of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase and c-fos immunoreactivity were performed. The effects of MK-801, an NMDA receptor blocker and $N^\omega$-nitro-L-arginine (L-NNA), a nitric oxide synthase (NOS) inhibitor were evaluated. Results: 1) Injection of CFA induced mechanical allodynia, mechanical hyperalgesia and thermal hyperalgesia. And it increased the number of NADPH-diaphorase positive neurons and c-fos expression neurons. 2) MK-801 inhibited mechanical hyperalgesia and thermal hyperalgesia induced by CFA and reduced the number of NADPH-diaphorase positive neurons and c-fos expression neurons. 3) L-NNA inhibited the thermal hyperalgesia and reduced the number of NADPH-diaphorase positive neurons, but did not affect the number of c-fos expression neurons. Conclusions: These results suggest that in the mechanism of mechanical hyperalgesia, NMDA receptor but not NO-system is involved and in the case of thermal hyperalgesia both NMDA receptor and NO system are involved. NO system did not affect the expression of c-fos, but c-fos expression and NOS activity were dependent on the activity of NMDA receptor.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.1
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• pp.1-8
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• 2016

Damage in the periphery or spinal cord induces maladaptive plastic changes along the somatosensory nervous system from the periphery to the cortex, often leading to chronic pain. Although the role of neural circuit remodeling and structural synaptic plasticity in the 'pain matrix' cortices in chronic pain has been thought as a secondary epiphenomenon to altered nociceptive signaling in the spinal cord, progress in whole brain imaging studies on human patients and animal models has suggested a possibility that plastic changes in cortical neural circuits may actively contribute to chronic pain symptoms. Furthermore, recent development in two-photon microscopy and fluorescence labeling techniques have enabled us to longitudinally trace the structural and functional changes in local circuits, single neurons and even individual synapses in the brain of living animals. These technical advances has started to reveal that cortical structural remodeling following tissue or nerve damage could rapidly occur within days, which are temporally correlated with functional plasticity of cortical circuits as well as the development and maintenance of chronic pain behavior, thereby modifying the previous concept that it takes much longer periods (e.g. months or years). In this review, we discuss the relation of neural circuit plasticity in the 'pain matrix' cortices, such as the anterior cingulate cortex, prefrontal cortex and primary somatosensory cortex, with chronic pain. We also introduce how to apply long-term in vivo two-photon imaging approaches for the study of pathophysiological mechanisms of chronic pain.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.05a
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• pp.14-23
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• 2002

Development of oligodendrocytes and the generation of myelin internodes within the spinal cord depends on regional signals derived from the notochord and axonally derived signals. Neuregulin (NRG)-1, localized in the floor plate as well as in motor and sensory neurons, is necessary for normal oligodendrocyte development. Oligodendrocytes respond to NRGs by activating members of the erbB receptor tyrosine kinase family. Here, we show that erbB2 is not necessary for the early stages of oligodendrocyte precursor development, but is essential for proligodendroblasts to differentiate into galactosylcerebroside-positive (GalC+) oligodendrocytes. In the presence of erbB2, oligodendrocyte development is normal. In the absence of erbB2 (erbB2-/-), however, oligodendrocyte development is halted at the proligodendroblast stage with a >10-fold reduction in the number of GalC+ oligodendrocytes. ErbB2 appears to function in the transition of proligodendroblast to oligodendrocyte by transducing a terminal differentiation signal, since there is no evidence of increased oligodendrocyte death in the absence of erbB2. Furthermore, known survival signals for oligodendrocytes increase oligodendrocyte numbers in the presence of erbB2, but fail to do so in the absence of erbB2. Of the erbB2-/- oligodendrocytes that do differentiate, all fail to ensheath neurites. These data suggest that erbB2 is required for the terminal differentiation of oligodendrocytes and for development of myelin.

• BMB Reports
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• v.55 no.12
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• pp.621-626
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• 2022

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by the degeneration of motor neurons in the spinal cord. Main symptoms are manifested as weakness, muscle loss, and muscle atrophy. Some studies have reported that alterations in sphingolipid metabolism may be intimately related to neurodegenerative diseases, including ALS. Acid sphingomyelinase (ASM), a sphingolipid-metabolizing enzyme, is considered an important mediator of neurodegenerative diseases. Herein, we show that ASM activity increases in samples from patients with ALS and in a mouse model. Moreover, genetic inhibition of ASM improves motor function impairment and spinal neuronal loss in an ALS mouse model. Therefore, these results suggest the role of ASM as a potentially effective target and ASM inhibition may be a possible therapeutic approach for ALS.

• Biomedical Science Letters
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• v.15 no.3
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• pp.261-263
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• 2009

Methylprednisolone is a synthetic glucocorticoid which is usually taken intravenously for many neurosurgical diseases which cause edema including brain tumor, and trauma including spinal cord injury. Methylprednisolone reduces swelling and decreases the body's immune response. It is also used to treat many immune and allergic disorders, such as arthritis, lupus, psoriasis, asthma, ulcerative colitis, and Crohn's disease. To identify genes expressed during methylprednisolone treatment against neurons of rats (PC12 cells), DNA microarray method was used. We have isolated 2 gene groups (up- or down-regulated genes) which are methylprednisolone differentially expressed in neurons. Lipocalin 3 is the gene most significantly increased among 772 up-regulated genes (more than 2 fold over-expression) and Aristaless 3 is the gene most dramatically decreased among 959 down-regulated genes (more than 2 fold down-expression). The gene increased expression of Fgb, Thbd, Cfi, F3, Kngl, Serpinel, C3, Tnfrsf4 and Il8rb are involved stress-response gene, and Nfkbia, Casp7, Pik3rl, I11b, Unc5a, Tgfb2, Kitl and Fgf15 are strongly associated with development. Cell cycle associated genes (Mcm6, Ccnb2, Plk1, Ccnd1, E2f1, Cdc2a, Tgfa, Dusp6, Id3) and cell proliferation associated genes (Ccl2, Tnfsf13, Csf2, Kit, Pim1, Nr3c1, Chrm4, Fosl1, Spp1) are down-regulated more than 2 times by methylprednisolone treatment. Among the genes described above, 4 up-regulated genes are confirmed those expression by RT-PCR. We found that methylprednisolone is related to expression of many genes associated with stress response, development, cell cycle, and cell proliferation by DNA microarray analysis. However, We think further experimental molecular studies will be needed to figure out the exact biological function of various genes described above and the physiological change of neuronal cells by methylprednisolone. The resulting data will give the one of the good clues for understanding of methylprednisolone under molecular level in the neurons.