• Korean Journal of Acupuncture
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• v.26 no.2
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• pp.75-89
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• 2009

Objectives: Warm needling combines simultaneously the effects of acupuncture and moxibustion. This study was to investigate whether warm needling could relieve acute knee arthritis induced by carrageenan in rats. Methods: To illuminate the underlying mechanisms of the warm needling-induced antinociception, weight bearing force (WBF) was observed on the acute knee arthritic rat model. Under general anesthesia, ST36, SP9, Hakjung extra point, LI4 were punctured and stimulated with 30 mg moxa ball combustion on top of the needle (${\emptyset}0.18{\times}8mm$). Results: In behavioral test, rats subsequently showed a reduced stepping force of the affected limb 3 hours after the induction of arthritis. Warm needling on the contralateral or ipsilateral ST36 failed to show antinociceptive effect on the acute knee arthritis. Warm needling on the contralateral SP9 or LI4 increased WBF values to normal level in the acute stage of the arthritis. Warm needling on the Hakjung extra-point resulted in the significant antinociceptive effects through acute stage. These effects of warm needling were suppressed by opioids receptor antagonist naltrexone (10 mg/kg, i.p.) and alpha adrenoceptor antagonist phentolamine (5 mg/kg, i.p.). Conclusion: The data suggest that warm needling-induced antinociception is differently mediated by acupoints and accomplished by activating the descending inhibitory systems including endogenous opioids and $\alpha$-adrenoceptors.

• Korean Journal of Acupuncture
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• v.22 no.3
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• pp.83-104
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• 2005

Objectives : DaeBangPungTang(DBPT) is one of the prescriptions used for the treatment of knee arthritis in oriental medicine. The present study aimed to examine the analgesic effect of DBPT on a rat model of carrageenan-induced arthritis, and the relations between DBPT-induced analgesia and endogenous nitric oxide(NO) and inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and c-Fos protein expression in the spinal cord. Methods : Carrageenan-induced arthritis rat model was used to test the effect of DBPT as a chronic pain model. After the induction of arthritis, rats subsequently showed a reduced stepping force of the affected limb for at least tile next 4 days. The reduced stepping force of the limb was presumably due to a painful knee, since oral infection of indomethacin produced temporary improvement of weight bearing. DBPT dissolved in normal saline was minted several acupoints. After the treatment, behavioral tests measuring stepping force were periodically conducted during the next 12 hours. Results : DBPT produced significant improvement of stepping force of the hindlimb affected by the arthritis lasting at least 9 hours. The magnitude of this improvement was equivalent to that obtained after an oral injection of 3mg/kg of indomethacin and this improvement of stepping force was interpreted as an analgesic effect. DBPT produced the improvement of stepping force of the affected hindlimb in a dose-dependent manner. Both NO production and iNOS, COX-2 protein expression increased by arthritis were suppressed by DBPT. DBPT on combination with electroacupuncture (EA) produced more powerful and longer lasting improvement of stepping force of the hindlimb affected by the arthritis than either DBPT or EA did. Conclusion : The present study suggest that DBPT produces a potent analgesic effect on the chronic hee arthritis pain model in the rat and that DBPT-induced analgesia modulate endogenous NO through the suppression of iNOS/COX-2 protein expression.

• Korean Journal of Acupuncture
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• v.23 no.1
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• pp.67-85
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• 2006

Obiecnves : The purpose of this study was to examine the analgesic effect of moxi-tar on a rat model of carrageenan-induced arthritis and the relations between moxi-tar-induced analgesia and endogenous NO and iNOS, cyclooxygenase-2 (COX-2), and c-Fos protein expression in the spinal cord. Methods : Carrageenan-induced arthritis rat model was used to test the effect of moxi-tar as a chronic pain model. After the induction of arthritis, rats subsequently showed a reduced stepping force of the affected limb for at least the next 4 days. The reduced stepping force of the limb was presumably due to a painful knee, since oral injection of indomethacin produced temporary improvement of weight bearing. Moxi-tar dissolved in ethyl alcohol was injected several acupoints. After the treatment, behavioral tests measuring stepping force were periodically conducted during the next 12 hours. Results : Moxi-tar produced significant improvement of stepping force of the hindlimb affected by the arthritis lasting at least 9 hours. The magnitude of this improvement was equivalent to that obtained after an oral injection of 3 mg/kg of indomethacin and this improvement of stepping force was interpreted as an analgesic effect. Moxi-tar produced the improvement of stepping force of the affected hindlimb in a dose-dependent manner. Both NO production and iNOS, COX-2 protein expression increased by arthritis were suppressed by moxi-tar. moxi-tar on combination with electroacupuncture (EA) produced more powerful and longer lasting improvement of stepping force of the hindlimb affected by the arthritis than either moxi-tar or EA did. Conclusion : The present study suggest that moxi-tar produces a potent analgesic effect on the chronic knee arthritis pain model in the rat and that moxi-tar-induced analgesia modulate endogenous NO through the suppression of iNOS/COX-2 protein expression.

• Korean Journal of Acupuncture
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• v.21 no.1
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• pp.113-127
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• 2004

Objectives : The usage of acupuncture has gained popularity as an alternative method of treatment for certain chronic pain conditions. However, the efficacy of acupuncture in various diseases has not been fully established and the underlying mechanism is not clearly understood. In the present study, the effect of electroacupuncture (EA) applied to foot samli$(ST_{36})$ on the carrageenan-induced knee arthritic pain was examined. Methods : A common source of persistent pain in humans is the knee arthritis. Knee arthritis was induced by injection of 2 % carrageenan $50\;{\mu}l$ into the knee joint cavity. When rats developed pain behaviors, EA was applied for 30 min. under enflurane anesthesia with repeated train stimuli at the intensity of 10X of muscle twitch threshold. The weight bearing force of the hind limb was measured for an indicator of pain level after each manipulation. Results : The average weight borne by the hind limb during normal gait was 55% of total body weight, which was reduced to less than 10% after knee arthritis. EA improved the weight bearing of the arthritic hind limb significantly for the duration of 4 hr. EA applied to $ST_{36}$ point produced a significant improvement of stepping force of the arthritic foot lasting for at least 4 h. However, $GB_{31}$ point did not produce any significant increase of weight bearing force. The analgesic effect was specific to the acupuncture point since the analgesic effect on the knee arthritis model could not be mimicked by EA applied to a nearby point, $GB_{31}$. The relations between EA-induced analgesia and endogenous nitric oxide(NO) and inducible NO synthase(iNOS)/neuronal NOS was also examined. Results were turned out that both NO production and nNOS/iNOS protein expression which is increased by arthritis were suppressed by EA stimulation applied to $ST_{36}$ point. Conclusions : The data suggest 1) that EA produces a potent analgesic effect on the rat model of chronic knee arthritis pain in a point specific manner and 2) that EA-induced analgesia modulate endogenous NO through the suppression of nNOS/iNOS protein expression.

• The Journal of Traditional Korean Medicine
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• v.15 no.1
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• pp.113-127
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• 2006

Objectives: This study was produced to examine the effects of moxibustion that had been played important role to traditional oriental medical treatment on disease. Recently, it was reported that moxi-tar which is generated in the process of moxibustion as burning combustibles decreased nitric oxide(NO) and inducible NO synthase (iNOS) generation in cellular experiments. Methods: Carrageenan-induced arthritis rat model was used to test the effect of moxi-tar as a chronic pain model. Diluted moxi-tar was single injected in several acupoints or combined with electroacupuncture (l ms, 2 Hz, and 2 mA) into contralateral ST36 acupoint for 30 min to assess the synergic effects. After the treatment, behavioral tests measuring stepping force were periodically conducted during the next 12 hours. Endogenous NO and iNOS, cyclooxygenase-2 (COX-2), and c-Fos protein expression in the spinal cord were examined on a rat model of carrageenan-induced arthritis. Results : After the induction of arthritis, rats subsequently showed a reduced stepping force of the affected limb for at least the next 4 days. The reduced stepping force of the limb was presumably due to a painful knee, since oral injection of indomethacin produced temporary improvement of weight bearing. Maxi-tar produced significant improvement of stepping force of the hindlimb affected by the arthritis lasting at least 9 hours. The magnitude of this improvement was equivalent to that obtained after an oral injection of 3 mg/kg of indomethacin and this improvement of stepping force was interpreted as an analgesic effect. Maxi-tar produced the improvement of stepping force of the affected hindlimb in a dose-dependent manner. Both NO production and iNOS, COX-2 protein expression increased by arthritis were suppressed by maxi-tar. Moxi-tar on combination with electroacupuncture (EA) produced more powerful and longer lasting improvement of stepping force of the hindlimb affected by the arthritis than either moxi-tar or EA did. Conclusion : The present study suggest that maxi-tar produces a potent analgesic effect on the chronic knee arthritis pain model in the rat and that moxi-tar-induced analgesia modulate endogenous NO through the suppression of iNOS/COX-2 protein expression.

• Biomolecules & Therapeutics
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• v.31 no.5
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• pp.536-543
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• 2023

Phytoceramide (Pcer) is found mainly in plants and yeast. It can be neuroprotective and immunostimulatory on various cell types. In this study, the therapeutic effect of Pcer was explored using the carrageenan/kaolin (C/K)-induced arthritis rat model and fibroblast-like synoviocytes (FLS). Pcer treatment (1, 10, and 30 mg/kg/day) were given to the arthritic rats for 6 days after disease induction. Weight distribution ration (WDR), knee thickness, squeaking score, serum levels of proinflammatory mediators, and histological analysis were measured and performed to evaluate arthritic symptoms in the rat model. In interleukin (IL)-1β-stimulated FLS, proinflammatory mediators were measured after Pcer (1-30 µM) treatment. Arthritic symptoms in rats with Pcer treatment were significantly decreased at days 4 to 6 after C/K arthritis induction. Inflammation in the knee joints were also significantly decreased in rats with Pcer treatment. Furthermore, in IL-1β-stimulated FLS, the expressions of proinflammatory mediators were also inhibited by Pcer. As shown by the results, Pcer has anti-arthritic effects in the C/K rat model and in synovial cells, suggesting that Pcer has the potential to be a useful agent in arthritis treatment.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.16 no.2
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• pp.138-151
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• 2003

Although the use of acupuncture for pain has increased in recent years, the mechanisms of acupuncture analgesia (AA) remains obscure. The lack of suitable experimental animal models for persistent pain, which show clear AA, has been the major stumbling block in the investigation of the physiological mechanisms of AA. In the present study, we test AA in two knee arthritis model induced by injection of CFA or carrageenan as a chronic pain model. After induction of arthritis, the rat subsequently showed a reduced stepping force of the affected limb for the next several days. Electroacupuncture (EA) was applied to an acupuncture point each on the contralateral forelimb for 30 minutes under enflurane anesthesia. After the termination of EA, behavioral tests measuring stepping force were periodically conducted during the next several hours. EA produced a significant improvement of stepping force of the foot lasting for at least 2 hours when applied to LR2 In CFA model, and applied to ST36 in carrageenan model, but both points did not produce any significant effects in each other model. These data suggest that EA produce analgesic effect in knee arthritic pain and the analgesic effect is specific to the acupuncture point.

• The Journal of Korean Physical Therapy
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• v.15 no.4
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• pp.299-311
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• 2003

The purpose of this study is to investigate and analysis effect of TENS with immunohistochemistry methode through changes of substance P in spinal using arthritis model after inducing inflammation. The changes of substance P induced at that time are compared with control which is not induced arthritis by means of counting. The effect of TENS (4Hz, $200{\mu}$, 20minutes) is also tested by observing changes of substance P in spinal dorsal horn after application on knee joint of rats which is arthritis model induced by kaolin and carrageenan. The results of this study were as follows: 1. Substance P immunoreactive positive neurons are increased in dorsal horn after inducting arthritis. 2. In arthritis group, Substance P immunoreactive positive neurons are progressively increased from the first to the third days. 3. Substance P immunoreactive positive neurons after applicating TENS on arthritis group are more decreased than only arthritis-induced group. 4. Substance P immunoreactive positive neurons were significantly decreased on the second days resulting from TENS application from the first to the third days. Therefore, TENS application is decrease Substance P immunoreactive positive neurons in spinal dorsal horn of rats induced arthritis. This decrease is considered as analgesic effect of TENS.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.6
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• pp.253-257
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• 2007

Among the arthritis symptoms, chronic pain is the most serious, and it can profoundly affect the quality of human life. Unfortunately, the mechanism of development in arthritis and arthritic pain has not yet been precisely elucidated. Accumulating evidence indicates that nitric oxide (NO) plays a pivotal role in nociceptive processing in the spinal cord. However, the modulation mechanism of NO in the peripheral site of arthritis and arthritic pain has not been clarified. Therefore, I determined in the present study which nitric oxide synthase (NOS) was involved in the induction of arthritis and arthritic pain. Monoarthritis was induced by intra-articular injection of carrageenan (2%, $50{\mu}l$) into rats, and resulted in the reduction of weight load on the injected leg, increase of knee joint diameter and inflammatory response. Pre-treatment of rats with L-N6-(1-iminoethyl)-lysine (L-NIL, $500{\mu}g$, in $50{\mu}l$), an inhibitor of inducible NOS (iNOS), partially prevented the induction of pain-related behavior and partially reduced inflammatory response in the synovial membrane in the knee joint. These results suggest that iNOS in the knee joint may play an important role in the induction of pain-related behavior and inflammation, and that NO produced by iNOS may be associated with nociceptive signaling in the peripheral site.

• Journal of Ginseng Research
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• v.45 no.5
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• pp.575-582
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• 2021

Background: In ginseng, there exists a glycolipoprotein complex with a special form of lipid LPAs called Gintonin. The purpose of this study is to show that Gintonin has a therapeutic effect on rheumatoid arthritis through LPA2 receptors. Methods: Fibroblast-like synoviocytes (FLS) were treated with Gintonin and stimulated with interleukin (IL)-1β. The antioxidant effect of Gintonin was measured using MitoSOX and H₂DCFDA experiments. The anti-arthritic efficacy of Gintonin was examined by analyzing the expression levels of inflammatory mediators, phosphorylation of mitogen-activated protein kinase (MAPK) pathways, and translocation of nuclear factor kappa B (NF-κB)/p65 into the nucleus through western blot. Next, after treatment with LPAR2 antagonist, western blot analysis was performed to measure inflammatory mediator expression levels, and NF-κB signaling pathway. Carrageenan/kaolin-induced arthritis rat model was used. Rats were orally administered with Gintonin (25, 50, and 100 mg/kg) every day for 6 days. The knee joint thickness, squeaking score, and weight distribution ratio (WDR) were measured as the behavioral parameters. After sacrifice, H&E staining was performed for histological analysis. Results: Gintonin significantly inhibited the expression of iNOS, TNF-α, IL-6 and COX-2. Gintonin prevented NF-κB/p65 from moving into the nucleus through the JNK and ERK MAPK phosphorylation in FLS cells. However, pretreatment with an LPA2 antagonist significantly reversed these effects of Gintonin. In the arthritis rat model, Gintonin suppressed all parameters that were measured. Conclusion: This study suggests that LPA2 receptor plays a key role in mediating the anti-arthritic effects of Gintonin by modulating inflammatory mediators, the MAPK and NF-κB signaling pathways.