• Journal of Acupuncture Research
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• 제20권4호
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• pp.11-23
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• 2003

Objective: In this study, the analgesic effect of gold injection aqua-acupuncture on CFA induced arthritis in rats was inverstigated. Furthermore, to determine the antinociceptive mechanism of gold injection aqua-acupuncture, naloxone and yohimbine were administrated intraperitoneally 15min prior to the gold injection aqua-acupuncture. Methods: The experimental groups were divided into 6 groups. Control group, NSI, AMI, AMI+SL : AMI+Nx, AMI+Yb. Thereafter we measured the chages of TFL between control and experimental groups. Results: 1. The tail flick latency induced by CFA was significantly increased on AMI as compared with the NSI group. 2. Effect of sodium aurothiomalate aqua-acupuncture in TFL on CFA was decreased after application of naloxone. The anti-nociceptive effect of AMI was completely antagonized by naloxone(an opioid receptor antagonist). 3. Effect of sodium aurothiomalate aqua-acupuncture in TFL on CFA was decreased after application of yohimbine. The anti-nociceptive effect of AMI was completely antagonized by yohimbine(${\alpha}2$-adrenoceptor antagonist). Conclusions: According to the results, gold injection aqua-acupuncture has significant analgesic effects on adjuvant induced arthritis in rats and the effect of anti-nociception was mediated by opiodergic system and ${\alpha}2$-adrenergic system.

• 생약학회지
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• 제26권2호
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• pp.139-147
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• 1995

Crinum asiaticum var. japonicum is a wild plant growing only in Jeju-island, Korea, and in Japan. The whole part of this plant has been known to have the pharmacological actions such as analgesic, anti-inflammatory, platelet-aggregation inhibitory, antitussive, and expectorant. With these assumed actions, the leaves (Crinum folium) of this plant has been used in the folk remedies for arthritis and arthralgia. There is, however, no scientific evidences for the pharmacological actions of Crinum asiaticum var. japonicum. In the present study, the analgesic, anti-inflammatory, and platelet-aggregation inhibitory actions of Crinium folium were evaluated using writhing test, tail-flick test, carrageenin antiedema test, in vitro thromboxane $B_2$ quantitation assay and in vitro platelet aggregation test. In order to obtain the partially purified fraction whose pharmacological action is excellent, the methanol extract of Crinium folium was fractionated consecutively into four biological fractions such as ether, ethyl acetate, butanol, and water fractions and their pharmacological actions of the fractions were investigated. Putting our results together, Crinium folium, especially ethyl acetate fraction was proven to have significant analgesic, anti-inflammatory and platelet-aggregation inhibitory actions by inhibition of prostanoids biosynthesis as one of its mechanism of action.

• 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

• The Korean Journal of Pain
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• 제32권2호
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• pp.79-86
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• 2019

Background: The use of aroma oils dates back to at least 3000 B.C., where it was applied to mummify corpses and treat the wounds of soldiers. Since the 1920s, the term "aromatherapy" has been used for fragrance therapy with essential oils. The purpose of this study was to determine whether the essential oil of Eucalyptus (EOE) affects pain pathways in various pain conditions and motor coordination. Methods: Mice were subjected to inhalation or intraperitoneal injection of EOE, and its analgesic effects were assessed by conducting formalin, thermal plantar, and acetic acid tests; the effects of EOE on motor coordination were evaluated using a rotarod test. To determine the analgesic mechanism, 5'-guanidinonaltrindole (${\kappa}$-opioid antagonist, 0.3 mg/kg), naltrindole (${\delta}$-opioid antagonist, 5 mg/kg), glibenclamide (${\delta}$-opioid antagonist, 2 mg/kg), and naloxone (${\mu}$-opioid antagonist, 4, 8, 12 mg/kg) were injected intraperitoneally. Results: EOE showed an analgesic effect against visceral pain caused by acetic acid (EOE, 45 mg/kg); however, no analgesic effect was observed against thermal nociceptive pain. Moreover, it was demonstrated that EOE did not have an effect on motor coordination. In addition, an anti-inflammatory effect was observed during the formalin test. Conclusions: EOE, which is associated with the ${\mu}$-opioid pain pathway, showed potential effects against somatic, inflammatory, and visceral pain and could be a potential therapeutic agent for pain.

• Journal of Acupuncture Research
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• 제22권1호
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• pp.99-108
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• 2005

Collagen 유발(誘發) 관절염(關節炎) 동물모델을 이용하여 족삼리(足三里) (ST36) 봉독약월(蜂毒藥鉞)의 진통효과(鎭痛效果)와 그 기전(機轉) 을 관찰하기 위하여 TFL을 지표로 하여 통증 역치의 변화와 naloxone 및 yohimbine으로 전처(前處) 치한(置) 후 (後) 봉독약침(蜂毒藥鍼)의 진통효과(鎭痛效果)를 관찰한 결과 다음과 같은 결론을 얻었다. 1. Collagen 유발(誘發) 관절염(關節炎)의 rat에서 TFL 통증 역치는 1, 2, 3 및 4주로 갈수록 지속적 감소를 나타내었다. 2. 1회와 2주간 봉독약철(蜂毒藥鐵)은 collagen 유발(誘發) 관절염(關節炎) rat의 통증역치를 각각 증가시켰다. 3. CIA rat에 opioid receptor antagonist인 naloxone을 투여한 후 봉독약침(蜂毒藥鍼)을 처치한 결과 진통효과(鎭痛效果)가 유지되는 것으로 보아 봉독약광(蜂毒藥鑛)의 진통기전(鎭痛機轉)은 아편양 기전(機轉)과 관련이 없는 것으로 사료된다. 4. CIA rat에 ${\alpha}2$-adrenoceptor antagonist인 ohimbine을 투여한 후 봉독약침(蜂毒藥鍼)을 처치한 결과 진통효과(鎭痛效果)가 길항(拮抗)되는 것으로 보아, 봉독약침(蜂毒藥鍼)의 기전(機轉)은 ${\alpha}2$-adrenoceptor에 의하여 매개는 것으로 사료된다.

• The Korean Journal of Pain
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• 제29권3호
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• pp.164-171
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• 2016

Background: Nefopam has been known as an inhibitor of the reuptake of monoamines, and the noradrenergic and/or serotonergic system has been focused on as a mechanism of its analgesic action. Here we investigated the role of the spinal dopaminergic neurotransmission in the antinociceptive effect of nefopam administered intravenously or intrathecally. Methods: The effects of intravenously and intrathecally administered nefopam were examined using the rat formalin test. Then we performed a microdialysis study to confirm the change of extracellular dopamine concentration in the spinal dorsal horn by nefopam. To determine whether the changes of dopamine level are associated with the nefopam analgesia, its mechanism was investigated pharmacologically via pretreatment with sulpiride, a dopaminergic D2 receptor antagonist. Results: When nefopam was administered intravenously the flinching responses in phase I of the formalin test were decreased, but not those in phase II of the formalin test were decreased. Intrathecally injected nefopam reduced the flinching responses in both phases of the formalin test in a dose dependent manner. Microdialysis study revealed a significant increase of the level of dopamine in the spinal cord by intrathecally administered nefopam (about 3.8 fold the baseline value) but not by that administered intravenously. The analgesic effects of intrathecally injected nefopam were not affected by pretreatment with sulpiride, and neither were those of the intravenous nefopam. Conclusions: Both the intravenously and intrathecally administered nefopam effectively relieved inflammatory pain in rats. Nefopam may act as an inhibitor of dopamine reuptake when delivered into the spinal cord. However, the analgesic mechanism of nefopam may not involve the dopaminergic transmission at the spinal level.

• Korean Journal of Acupuncture
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• 제30권4호
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• pp.220-229
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• 2013

Objectives : Electroacupuncture(EA) has been used effectively in producing analgesia on ankle sprain pain of humans and animals. Currently to examine the underlying mechanisms of the EA-induced analgesia, the effects of EA on weight-bearing forces(WBR) were examined at ankle sprain classified as grade 3 in rats. Methods : The severe ankle sprain classified as grade 3 was induced surgically by ankle ligament injury in the Sprague-Dawley rats. WBR of the affected foot were examined to evaluate effects and mechanism of EA(2 Hz, 1 ms pulse width, 2 mA intensity, for 15 min) which was applied to either SI6, GB34, or GB39 acupoints. The rats were pretreated with naltrexone(10 mg/kg, i.p.) as an opioid receptor antagonist or phentolamine(5 mg/kg, i.p) as an ${\alpha}$-adrenoceptor antagonist at 30 min before EA. Results : The daily repeat EA at either SI6, GB34, or GB39 showed significant analgesic effects on the severe ankle sprain. Particularly, daily EA at GB34 showed more potent analgesic effect than the others. In addition, the naltrexone pretreatment completely blocked the analgesic effect of EA at GB34, indicating the involvement of the endogenous opioid system in mediating the effect of EA at GB34. However, the phentolamine pretreament blocked analgesic effects of EA at either SI6 or GB39, indicating the involvement of ${\alpha}$-adrenoceptors in mediating the effect of EA at either SI6 or GB39. Conclusions : These data suggest that EA-induced analgesia on ankle sprain pain is mediated through either endogenous opioids or ${\alpha}$-adrenoceptors dependant on acupoint specific pattern.

• The Korean Journal of Pain
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• 제27권1호
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• pp.23-29
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• 2014

Background: Nefopam has shown an analgesic effect on acute pain including postoperative pain. The reuptake of monoamines including serotonin and noradrenaline has been proposed as the mechanism of the analgesic action of nefopam, but it remains unclear. Although alpha-adrenergic agents are being widely used in the perioperative period, the role of noradrenergic modulation in the analgesic effect of nefopam has not been fully addressed. Methods: Changes in the antinociceptive effect of intrathecal (i.t.) nefopam against formalin-elicited flinching responses were explored in Sprague-Dawley rats pretreated with i.t. 6-hydroxydopamine (6-OHDA), which depletes spinal noradrenaline. In addition, antagonism to the effect of nefopam by prazosin and yohimbine was evaluated to further elucidate the antinociceptive mechanism of i.t. nefopam. Results: Pretreatment with i.t. 6-OHDA alone did not alter the flinching responses in either phase of the formalin test, while it attenuated the antinociceptive effect of i.t. nefopam significantly during phase 1, but not phase 2. The antagonist of the alpha-2 receptor, but not the alpha-1 receptor, reduced partially, but significantly, the antinociceptive effect of i.t. nefopam during phase 1, but not during phase 2. Conclusions: This study demonstrates that spinal noradrenergic modulation plays an important role in the antinociceptive effect of i.t. nefopam against formalin-elicited acute initial pain, but not facilitated pain, and this action involves the spinal alpha-2 but not the alpha-1 receptor.

• Natural Product Sciences
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• 제9권4호
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• pp.256-259
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• 2003

The pet ether extract of Caesalpinia pulcherrima, leaves was studied for its antinociceptive, anti-inflammatory and antipyretic property. The extract at doses of 50 and 200 mg/kg, p.o., significantly (p<0.05) reduced the number of writhing induced by acetic acid and inhibited the late phase (20-30 min) in formalin test in mice. The extract failed to increase the pain threshold level in tail immersion test in mice. In carrageenan induced paw edema in rats and in acetic acid induced increase in vascular permeability test in mice, the extract (50-600 mg/kg, p.o.) failed to produce any significant activity. While in cotton pellet granuloma test, the extract at doses of 200 and 600 mg/kg (p.o.) significantly (p<0.05) reduced the granuloma formation and was comparable to reference drug, dexamethasone. In ethylpheylpropiolate ear edema test 0.5 mg and 1 mg/ear application of extract significantly (p<0.05) inhibited ear edema. In yeast induced hyperthermia in rats, the extract did not produce any reduction in temperature. The results suggest that the extract acts peripherally to produce analgesic action and anti-inflammatory activity through steroidal mechanism.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.339.3-340
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• 2002

Capsaicin is hot taste ingredient of chili pepper and was isolated in 1876 and in 1919 its structure is sympathized compound. induces pain and when persistently dosed. the fact will bring insensible condition to other chemical and mechanical thermal stimulation by incapacitating sensory neuron is known. The analgesic effect by desensitization of such capsaicin is differ from the mechanism by analgesic action by opiate receptor of the existing analgesia or by prostaglandin mediation and the efficacy was known as similar with morphine. (omitted)