• The Korean Journal of Physiology and Pharmacology
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• v.17 no.2
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• pp.121-125
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• 2013

The purpose of this study is to investigate the antinociceptive effects of ginsenosides on toothache. c-Fos immunoreactive (IR) neurons were examined after noxious intrapulpal stimulation (NS) by intrapulpal injection of 2 M KCl into upper and lower incisor pulps exposed by bone cutter in Sprague Dawley rats. The number of Fos-IR neurons was increased in the trigeminal subnucleus caudalis (Vc) and the transitional region between Vc and subnucleus interpolaris (Vi) by NS to tooth. The intradental NS raised arterial blood pressure (BP) and heart rate (HR). The number of Fos-IR neurons was also enhanced in thalamic ventral posteromedial nucleus (VPMN) and centrolateral nucleus (CLN) by NS to tooth. The intradental NS increased the number of Fos-IR neurons in the nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM), hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN), central cardiovascular regulation centers. Ginsenosides reduced the number of c-Fos-IR increased by NS to tooth in the trigeminal Vc and thalamic VPMN and CLN. Naloxone, an opioid antagonist, did not block the effect of ginsenoside on the number of Fos-IR neurons enhanced by NS to tooth in the trigeminal Vc and thalamic VPMN and CLN. Ginsenosides ameliorated arterial BP and HR raised by NS to tooth and reduced the number of Fos-IR neurons increased by NS to tooth in the NTS, RVLM, hypothalamic SON, and PVN. These results suggest that ginsenosides have an antinociceptive effect on toothache through non-opioid system and attenuates BP and HR increased by NS to tooth.

• Molecules and Cells
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• v.27 no.4
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• pp.417-422
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• 2009

Lipoxygenase (LO) metabolites are generated in inflamed tissues. However, it is unclear whether the inhibition of the LO activity regulates the expression of c-Fos protein, a pain marker in the spinal cord. Here we used a carrageenan-induced inflammation model to examine the role of LO in the development of c-Fos expression. Intradermally injected carrageenan caused elevated number of cells exhibiting Fos-like immunoreactivity (Fos-LI) in the spinal dorsal horn, and decreased the thermal and mechanical threshold in Hargreaves and von Frey tests. Pretreatment with an inhibitor of phospholipase A2, that generates the LO substrate, prior to the carrageenan injection significantly reduced the number of Fos-(+) cells. A general LO inhibitor NDGA, a 5-LO inhibitor AA-861 and a 12-LO inhibitor baicalein also exhibited the similar effects. Moreover, the LO inhibitors suppressed carrageenan-induced thermal and mechanical hyperalgesic behaviors, which inidcates that the changes in Fos expression correlates with those in the nociceptive behaviors in the inflamed rats. LO products are endogenous TRPV1 activators and pretreatment with BCTC, a TRPV1 antagonist inhibited the thermal but not the mechanical hypersensitivity. Overall, our results from the Fos-LI and behavior tests suggest that LO products released from inflamed tissues contribute to nociception during carrageenan-induced inflammation, indicating that the LO pathway is a possible target for modulating inflammatory pain.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.4
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• pp.299-305
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• 2001

Activation of D1-like dopamine receptors by psychostimulants, such as amphetamine, upregulates the expression of immediate early gene and opioid peptide gene in the striatum. The genomic changes are regulated by phosphorylated transcription factors via complicated intracellular events. To evaluate temporal expression of the transcription factors by dopaminergic stimulation, the D1-like dopamine agonist, amphetamine or SKF82958, was systematically delivered. As intracellular markers in response to the agonist, phosphorylated cAMP response element-binding protein (pCREB), Fos-related antigens (FRA) and FosB immunoreactivity (IR) was compared at 20 and 120 min time points in the selected areas of the striatum. Semi-quantitative immunocytochemistry showed that amphetamine (5 mg/kg, i.p.) significantly increased pCREB-IR at 20 min, sustained up to 60 min and decreased at 120 min after the infusion. Like amphetamine, the full D1 agonist, SKF82958 (0.5 mg/kg, s.c.), also increased pCREB-IR at 20 min, but not at 120 min after the infusion in the dorsal striatum (caudoputaman, CPu) and shell of ventral striatum (nucleus accumbens, NAc). In contrast, FRA- and FosB-IR induced by SKF82958 was significantly increased at 120 min, but not at 20 min after the administration. These data indicate that SKF82958 mimics induction of CREB phosphorylation by amphetamine and differentially regulates temporal induction of pCREB, and FRA and FosB expression in the striatum.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.1
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• pp.75-80
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• 2005

The purpose of study is that we will observe the change of c-fos and CGRP with the immunohistochemistry method and then we will study the effect of microcurrent stimulation following the frequency after inducing pain to rats with capsaicin. The experimental groups were divided by microcurrent application and pain induce. Normal control groups is used in experiment I, the group which we induce pain is used in experiment II, the application group which we induce pain and then the high frequency microcurrent stimulation is used in experiment III, the application group which we induce pain and then the low frequency microcurrent stimulation is used in experiment IV. c-fos was strongly expressed after pain induced 2 hours and positive neurons were decreased from 2 hours. At 7 days, positive neuron recovers to normal range, But c-fos positive neuron of microcurrent stimulation group were decreased from 2 hours. CGRP was strongly expressed after pain induced 24 hours, and positive neurons were decreased from 7 days. These results suggests that microcurrent stimulation therapy effect to control pain according to expression of c-fos and CGRP examined by immunohistochemistry. Also high frequency microcurrent stimulation is more effective than low frequency microcurrent stimulation for controling the pain.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.1
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• pp.224-229
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• 2005

Ginseng radix, the root of Panax ginseng C.A.Meyer (Araliaceae), has traditionally been used for the treatment of various disorders including cerebrovascular accident (CVA). In the present study, the effect of Ginseng radix on c-Fos expression and apoptosis in the hippocampal CA1 region of gerbils following transient global ischemia was investigated via immunohistochemistry for c-Fos and caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Enhanced c-Fos-, TUNEL-, and caspase-3-positivities were detected in the hippocampal CA1 region in ischemic gerbils. Administration of the aqueous extract of Ginseng radix suppressed this ischemia-induced increment in the numbers of c-Fos-, TUNEL-, and caspase-3-positive cells. These results suggest that Ginseng radix has an inhibitive effect on the induction of c-Fos expression and apoptosis seen following transient global ischemia.

• BMB Reports
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• v.32 no.6
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• pp.594-598
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• 1999

The Jun and Fos families of eukaryotic transcription factors form heterodimers capable of binding to their cognate DNA enhancer elements. We are interested in searching for inhibitors or antagonists of the binding of the Jun-Fos heterodimer to the activator protein-1 (AP-1) site. The basic-region leucine zipper (bZIP) domain of c-Fos was expressed as a fusion protein with glutathione S-transferase, and allowed to form a heterodimer with the bZIP domain of c-Jun. The heterodimer was bound to glutathione-agarose, to which were added radiolabeled AP-1 nucleotides. After thorough washing, the gel-bound radioactivity was counted. The assay is faster than the coventional electrophoretic mobility shift assay because the gel electrophoresis step and the autoradiography step are eliminated. Moreover, the assay is very sensitive, allowing the detection of picomolar quantities of nucleotides, and is not affected by up to 50% dimethylsulfoxide, a solvent for hydrophobic inhibitors. Curcumin and dihydroguaiaretic acid, recently known inhibitors of Jun-Fos-DNA complex formation, were applied to this Jun-GST-fused Fos system and revealed to decrease the dimer-DNA binding.

• The Journal of Korean Medicine
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• v.29 no.1
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• pp.39-46
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• 2008

Background : Acupuncture has been used as a clinical treatment in Oriental medicine for various diseases including pain relief. The descending pain control system of periaqueductal gray (PAG) is a powerful pain control system in mammalians. Expression of c-Fos is used as a marker for stimuli-induced metabolic changes of neurons. Objective : In the present study, the effects of acupuncture on analgesic effect in visceral pain were investigated through the writhing reflex and c-Fos expression in ventrolateral PAG (vlPAG) area using immunohistochemistry in mice. Method : For the writhing test, mice were divided into five groups. Immediately after finishing the behavioral test, the animals were weighed and overdosed with Zoletil. After a complete lack of response was observed, the brains of the mice were dissected into serial coronal sections, and c-Fos immunohistochemistry was performed. Statistical analysis of all data was performed using one-way ANOVA. Result : The present results showed that acupuncture affected the writhing reflex and that Choksamni (zusnali) acupoint and aspirin significantlysuppressed acetic acid treatment-induced increased writhing reflex, and the expression of c-Fos in vlPAG was significantly increased in the acupunctured group. Conclusion : The present study suggests that acupuncture has an antinociceptive effect on acetic acid-induced visceral pain by increase of c-Fos expression in mice. Aspirin also showed analgesic effect, however the mechanism is different from the acupuncture.

• BMB Reports
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• v.34 no.1
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• pp.28-32
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• 2001

The Fos-Jun heterodimers are part of the regulatory network of gene expression and nuclear proteins encoded by proto-oncogenes. The activation of Fos-Jun is important in the transmission of the tumor-promoting signal from the extracellular environment to the nuclear transcription mechanism. To search for the inhibitors of the Fos-Jun DNA complex formation, several natural products were screened and water-soluble paeoniflorin reduced the binding activity of the Fos-Jun heterodimer. This active compound was purified by silica gel column chromatography and HPLC. The electrophoresis mobility shift assay and reverse-phase HPLC test showed that paeoniflorin reduced the AP-l function. The cytotoxic effect of paeoniflorin was observed in HL-60. These results indicate that paeoniflorin blocks the Fos-Jun heterodimer-binding site of the AP-l DNA and it also has cytotoxic effects on human leukemia cell lines.

• Herbal Formula Science
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• v.17 no.1
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• pp.129-140
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• 2009

Objectives : The goal of this study was to investigate the effect of Moutan Cortex as antidepressant in forced swimming test(FST) model. Methods : The expressions of corticotropin-releasing Factor(CRF), c-Fos and tyrosine hydroxylase(TH) were measured with immunohistochemical method at paraventricular nucleus (PVN), locus coeruleus(LC) and ventral tegmental area(VTA). Results : The duration of immobility in the forced swimming test was significantly decreased in the Moutan Cortex 100 mg/kg treated group in comparison with the control group(p<0.01). CRF and c-Fos expressions at PVN were decreased in the Moutan Cortex 100mg/kg treated group in comparison with the control group. But only the expression of c-Fos was shown the significance(p<0.05). TH expressions at LC and VTA were significantly decreased in the Moutan Cortex 100mg/kg and 400mg/kg treated group in comparison with the control group(p<0.001). Conclusion : According to the results, Moutan Cortex has the antidepressant effect by showing the reduced immobility through the reduction of c-Fos expression at PVN and the reduction of TH expression at LC and VTA.

• The Journal of Korean Physical Therapy
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• v.15 no.4
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• pp.190-198
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• 2003

Expression of c-fos, an immediate early gene, has accepted to be a marker of functional activity in neurons. This study was aimed to investigate the effects of cold therapy on the expression of spinal cord c-fos in rats of carrageenan-induced muscle pain. Muscle pain was induced in male Sprague-Dawley rats by intra-muscular injection of gastrocnemius with $2\%$ carrageenan. The paw withdrawal latency (PWL) and tail flick test (TFT) responses to heat stimuli were used to detect secondary hyperalgesia produced by the muscle pain and measured to assess the effects of cold. The expression of c-fos was determined in the lumbar regions of the spinal cord by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry assays. The secondary hyperalgesia to heat simuli (PWL and TFT) were significantly reduced in cold therapy compared with that in the controls. In RT-PCR assays the expression of c-fos mRNA was down-regulated in the lumbar spinal cord in cold group. In addition, Fos immunoreactivity in the dorsal horn of the lumbar spinal cord was decreased in cold group. These results suggested that application of cold attributed to increase PWL and TFT responses and to decrease expression of the c-fos produced by muscle pain.