• 대한약학회:학술대회논문집
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• 대한약학회 2000년도 춘계총회 및 학술대회
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• pp.70-81
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• 2000

DA-5018 is a synthetic capsaicin derivative under development as a non-narcotic a analgesic ag$\varepsilon$nt. DA-50 18 showed a potent analgesic activity against acute and chronic pain m model(Tablel, 2.), but it had a narrow margin of safety. DA-5018 did not bind to opioid(${\kappa}, {\delta}, {\mu}$), NKl, CGRP receptors in vitro and its analgesic effect was not antagonized by naloxone, a and it did not develop analgesic tolerance. In addition DA-5018 had no inhibitory effects against c cyclooxygenase and 5-lipooxygenase activities. DA-5018 significantly increased the relcase of substance P from the slices of the rat spinal cord. These results suggest that DA-50 18 is not a narcotic nor aspirin-like analgesic and the release of substance P is one of analgesic mechanism of action of DA-5018. We found that DA-5018 was almost ten times more potent and was at l least IOO-times less irritable compared to capsaicin. Accordingly development of topical formula was adopted. Topical formula was desiged and screened by flux test of DA-5018 using hairless mouse skin and several formulas were selected. With these topical formulas we a assessed the analgesic efficacy and carried out the toxicity, skin irritation and pharmacokinetic studies. In streptozotocin-induced hyperalgesic rat and 50 % galactose-fed hyperalgesic rat as diabetic pain models, DA-5018 cream increased the pain thresh이ds up to 77.0% and 24.4% respectively, while Zostrix-HP(capsaicin cream) incr$\varepsilon$as cd by 65.9% and 21.0%. DA-5018 c cream showed a good analgesic effect as welI in FCA-induced arthritic rat. DA-5018 cream did not show any toxicological signs in acute and chronic toxicity test and had little skin irritation in car swclIing and scratching t$\varepsilon$st. Pharmacokinetics of DA-50 18 were studied after topical application of ${14}^C$-Iabelled or unlabelIed DA-5018 cream. Plasma and skin concentrations c except applied skin wcre below the dctection limit and after 7-day cummulative application, plasma concentrations were also below detection limit DA-50 18 may have an advantag$\varepsilon$ ov$\varepsilon$r c capsaicin and is now being developed as a topical agent for the treatment of pains. DA-50 18 cream was approved for Korean IND and is now under a Phase II clinical study for arthritic pain a after finising Phase I study. DA-50 18 was also liscensed out to Stiefel Company in America in

• 근관절건강학회지
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• 제5권1호
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• pp.72-82
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• 1998

The purpose of this study was to identify functional impairment and psychological status and to analyze their relationships in patients with chronic arthritis. The sample was consisted of 75 arthritic patients who visited H hospital and S welfare center. Functional impairment was measured by ADL, pain, and the number of painful joint. Psychological status was measured by depression, self-efficacy, and quality of life. Data was analyzed by frequency, mean ${\pm} SD$, Pearson's correlation coefficient, and Stepwise multiple regression. The results of this study were as follows : 1. In functional Impairment, ADL was below average which means somewhat difficult, pain was above average, and the number of painful joint was 9.20. 2. In psychological status, scores of quality of life was 97.89, depression was 41.28, self-efficacy was 895.35. 3. Pain was negatively correlated to self-efficacy, ADL and quality of life, and positively correlated to depression. 4. Self efficacy and depression explained 45% of the variance in quality of life. Therefore, it is suggested that nursing intervention improving psychological status would be useful for patients with chronic arthritis. Especially, it is very important to implement nursing intervention focused on increasing self-efficacy and decreasing depression.

• The Korean Journal of Physiology and Pharmacology
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• 제20권1호
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• pp.129-136
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• 2016

This study was performed to investigate whether an intra-articular injection of transient receptor potential vanilloid 1 (TRPV1) receptor agonist, resiniferatoxin (RTX) would alleviate behavioral signs of arthritic pain in a rat model of osteoarthritis (OA). We also sought to determine the effect of RTX treatment on calcitonin gene-related peptide (CGRP) expression in the spinal cord. Knee joint inflammation was induced by intra-articular injection of monosodium iodoacetate (MIA, $8mg/50{\mu}l$) and weight bearing percentage on right and left hindpaws during walking, paw withdrawal threshold to mechanical stimulation, and paw withdrawal latency to heat were measured to evaluate pain behavior. Intra-articular administration of RTX (0.03, 0.003 and 0.0003%) at 2 weeks after the induction of knee joint inflammation significantly improved reduction of weight bearing on the ipsilateral hindlimb and increased paw withdrawal sensitivity to mechanical and heat stimuli. The reduction of pain behavior persisted for 3~10 days according to each behavioral test. The MIA-induced increase in CGRP immunoreactivity in the spinal cord was decreased by RTX treatment in a dose-dependent manner. The present study demonstrated that a single intra-articular administration of RTX reduced pain behaviors for a relatively long time in an experimental model of OA and could normalize OA-associated changes in peptide expression in the spinal cord.

• The Korean Journal of Pain
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• 제13권1호
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• pp.1-7
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• 2000

Background: Intraarticular local anesthetic injection has been therapeutically applied for pain control in various arthritis patients. However, little physiologic effects of local anesthetics on their tissue were known. This study was conducted to determine its effects on the cell proliferation and matrix metalloproteinases (MMP) production of cultured fibroblast like synoviocytes (FLS) derived from synovial tissues of rheumatoid arthritis patients. Methods: Bupivacaine with varying concentrations 0 (control), 0.1, 0.25, 0.5% was applied to experimental cell groups growing as monolayers in culture plates for varying durations 0 (control), 30, 90, 180 seconds in the presence and absence of interleukin-$1\beta$. Results: No statistical significances were noted in thymidine incorporation between 0, 30, 90 and 180 seconds exposure groups with 0.5% bupivacaine after 1 day and 2 days. Thymidine incorporation between 0, 0.1, 0.25, 0.5% exposure groups 1 day and 2 days after 90 seconds exposure did not show any differences. After exposure to bupivacaine, there were statistically significant increases in MMP-1 (p=0.025) and MMP-3 productions (p=0.000) of FLS in the absence of IL-$1\beta$, but no differences among the groups in the presence of IL-$1\beta$. Conclusion: We concluded that in this short-term in vitro study, bupivacaine does not have injurious effect on cultured rheumatoid arthritic joint tissues. The long-term effect cannot be known from this investigation.

• 근관절건강학회지
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• 제14권1호
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• pp.77-84
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• 2007

Purpose: The purpose of the study was to compare the effects of Tai Chi exercise, Tai Chi self help program, and self help management program on arthritic pain, stiffness, fatigue and difficulties in performing daily activities in patients with osteoarthritis. Method: The pre-post experimental design was utilized with convenient sampling at Public Health Centers. Total of 38 subjects agreed to participate in the study with the inclusion criteria of being diagnosed as osteoarthritis and no previous regular exercise. The 12 subjects were assigned to Tai Chi exercise group, 13 subjects to Tai Chi exercise combined with self help management program, and the other 13 to self help management program. Tai Chi exercise group performed exercise twice a week for one hour per each session. Tai Chi self help management group came to the class twice a week, one hour for Tai Chi exercise, and another hour for self help management program. The third group came to the class once a week for one hour to participate self help management program. At the completion of 6 week programs, 10 subjects from Tai Chi exercise, 9 from Tai Chi self help, another 10 from self help management groups completed the post-test measures. The data were analyzed by SPSSWIN 11.0. The homogeneity tests for three experimental groups were conducted by $X^2-test$, Fisher's exact test, Kruskal-Wallis test. The final analysis of the post-test measures was conducted by ANCOVA with fatigue, pain, stiffness, and difficulties in daily activities of the pretest measures as covariates. Results: The results were as follows. There were no significant differences in fatigue, pain, and difficulties of daily activities among three groups for the pretest measures. The score of arthritic stiffness was significantly different among groups after controlled for covariates, but the post-hoc tests showed no group differences. Conclusion: The nursing interventions applied for osteoarthritis patients have been previously tested to show the cost effectiveness of symptoms management of this population.

• Journal of Acupuncture Research
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• 제24권2호
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• pp.211-220
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• 2007

Objectives : This study was to investigate the effect of high frequency electroacupuncture at $ST_{36}$ acupuncture point on the Complete Freund's Adjuvant (CFA) induced rat arthritis pain model. Methods : Arthritis was induced by intradermal injection of CFA into base of tail. Experimental groups were divided into 4 groups; Normal, Control and Jok-Samri ($ST_{36}$) and Non-Acupuncture point (NA). Normal group, non-arthritic group, was injected with normal saline，and the others groups were injected CFA. $ST_{36}$ group was treated by 120 Hz electroacupuncture at $ST_{36}$ acupuncture point, and NA group was treated by 120 Hz electroacupuncture at non-acupuncture point. Each groups were evaluated by the change of c-fos positive neurons in periaqueductal gray (PAG) and hippocampus by using an image analyzer and a microscope. Results: - In the PAG region, the number of fos-positive cells in the $ST_{36}$ group ($42.37{\pm}5.08$) were significantly (p<0.05) decreased compared with the control group ($64.56{\pm}6.35$). - In the PAG region, the number of fos-positive cells in the NA group were meaninglessly decreased compared with the control group - In the Cornu Ammonis(CA)l region of hippocampus, the number of fos-positive cells in the $ST_{36}$ group ($7.00{\pm}1.08$) and NA group ($5.56{\pm}2.01$) were significantly (p<0.05) decreased compared with the control group ($13.81{\pm}1.24$). - In the dentate gyrus region of hippocampus, the number of fos- positive cells in the $ST_{36}$ group ($10.75{\pm}0.98$) and NA group ($6.56{\pm}0.78$) were significantly (p$26.45{\pm}1.82$). Conclusions : It is expected that high frequency electroacupuncture can be used a treatment of arthritic pain.

• 대한족부족관절학회지
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• 제12권1호
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• pp.86-92
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• 2008

Purpose: To evaluate the safety and prognostic factors of intramedullary nailing of distal tibia fractures in terms of function and symptoms of the ankle joint. Materials and Methods: We retrospectively analyzed 22 distal tibial fractures with intramedullary nailing. The mean duration of follow-up was 43 months. We reviewed medical records to describe each case. We measured radiographic parameters such as fracture configuration, arthritic change of the ankle joint and status of reduction. We also assessed clinical results by AOFAS ankle hind foot scoring system, degree of pain by VAS and range of motion to find out prognostic factors for functional result of the ankle joint. Results: Bone healing was obtained in all cases without any wound complications. Mean AOFAS ankle score was 94. There were 4 cases with mild (VAS<3/10) ankle pain and 2 cases with mild limitation of ankle motion. The comminution of fracture had a significant relationship with delayed angular deformity of ankle joint (p=0.032). There was no other significant parameter affecting ankle joint function except the location of nail-end. Conclusion: Intramedullary nailing in distal tibia fracture is a safe and effective procedure. But further study may need to evaluate the relationship between the position of nail-end and the function of ankle joint.

• Journal of Oral Medicine and Pain
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• 제39권3호
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• pp.100-106
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• 2014

Purpose: This study was performed to investigate the relationship between temporomandibular disorders (TMDs) and the asymmetry of the mandibular height. Methods: We compared 100 randomly selected TMD patients diagnosed by the research diagnostic criteria for TMD (RDC/TMD) Axis I with 100 non-TMD control subjects matched with the TMD patients in age and gender. The mandibular heights were measured on an orthopantomogram and the asymmetry index (AI) was calculated as previously described. Results: The absolute AI value of 4.37% turned out to be the least cut-off value defining asymmetry, which showed a significant difference in asymmetry incidence (p<0.01) between the TMD and control groups. The risk of TMD increased in the asymmetry group by 4.57 (odds ratio). The incidence of asymmetry was not related to age and gender in both of the TMD and control groups. When dividing the TMD group according to the RDC/TMD Axis I diagnosis, neither the incidence of muscle disorder nor disk displacement was related to the incidence of asymmetry. However, a higher incidence of asymmetry was observed in the subjects classified into the arthrosis/arthritis groups (p<0.01). Conclusions: Although it does not imply a direct cause-and-effect relationship, asymmetry resulting in more than 4.37% difference between mandibular heights may increase the risk of TMD and correlates positively to the incidence of arthritic change in the temporomandibular joint of TMD patients.

• 동의생리병리학회지
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• 제23권1호
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• pp.113-120
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• 2009

This study was performed to investigate the effects in inflammatory and pain status on rheumatoid arthritis(RA) induced rats by swimming exercise and Achyranthes Radix(AR) extracts ointment according to the application methods with the change of motor-behavioral and histochemistry study through the change of safranin o-fast green stain in the knee joint and prostaglandin $E_2(PGE_2)$ concentration production in serum for 28 days. They were randomly divided into four groups; Group I: RA induction, Group II: application of only swimming exercise after RA induction, Group III: application of only AR extracts ointment after RA induction, Group IV: application of both AR extracts ointment and swimming exercise after RA induction. The following results were obtained. Volume change of hind paw edema and arthritis indices test and arthritic dorsal flexion & plantar flexion pain test, group II, III, IV were showed that significantly decrease to each scores compared with group I (p<.01). Safranin o-fast green stain were showed histological indices, group II, III, IV were showed that significantly decrease the scores of cellular infiltration and synovial hyperplasia(p<.05), pannus formation and cartilage destruction(p<.01) compared with group I. Group IV were the most decreased compared with group II, III. The $PGE_2$ concentration of the group II, III, IV were decreased compared to the group I (p<.01) In conclusion, swimming exercise and AR extracts ointment acts were the most therapeutic intervention in inflammatory and pain control of RA induced rats.

• 한국한의학연구원논문집
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• 제12권3호통권18호
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• pp.49-58
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• 2006

Although the usage of acupuncture for pain has increased in recent years, the mechanisms of acupuncture analgesia (AA) remain unclear. 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 models induced by injection of CFA or carrageenan as persistent pain models. 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 gaseous 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. Further experiments showed that intraperitoneal pretreatment of naltrexone, a non-selective opioid antagonist, did not reduced the EA-induced improvement of stepping force in both of two models. These data suggest that EA produce analgesic effect in knee arthritic pain and the analgesic effect is specific to the acupuncture point depending on painful conditions.