• Biomolecules & Therapeutics
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• v.5 no.1
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• pp.94-99
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• 1997

Capsaicin is known to be an analgesic agent, affecting the synthesis, storage, , transport and release of substance p, the principal neurotransmitter of pain from periphery to the central nervous system(CNS). DA-5018, a newly synthesized capsaicin derivative has shown potent analgesic effect comparable to that of morphine in various rat models of experimentally inducted acute pairs. In this study the mechanism of analgesic actlvity of DA-5018 was examined. First, the electrically-evoked contraction of guinea pig trachea was inhibited by DA-5018 and these inhibition was recovered by incubation with capsafepine(3$\muM$), capsaicin receptor antagonist and this result suggested that DA-5018 has affinity on capsaicin receptor. The correlation between the norciceptive threshold and the release of substance P was evaluated. In vivo perfusion of slices of the rat spinal cord with DA-5018(10, 100$\muM$) produced a significant increase of the release of substance P and this increase was less than that of capsaicin(10$\muM$). The norciceptive threshold of rat treated with DA-5018(1 mg/kg, p.o) in tall pinch test increased from 2.9$\pm$0.3 to 23.5 $\pm$6.61. Tail pinch latency increased to a maximun at 15 min after DA-5018 treatment and then declined to control values by 120 min. The capsaicin-evoked release ot substance P from the spinal cord slices of rat treated with DA-5018 reduced from 2.38$\pm$ 0.79 to 0.69$\pm$ 0.26 pg/mg wet weight. This reduction reached to a minium at 15 min after DA-5018 treatment and then recovered to control value by 120 min. These results mean that analgesic activity of DA-5018 is due to release of substance P The effect of DA-5018 cream on electrically-evoked neurogenic inflammation of rat saphenous nerve was compared with capsaicin (zostrix-HP). DA-5018 showed 34% inhibition of the neurogenic extravasation while capsaicin showed significant 67% inhibition. This result indicates that the potency of DA-5018 in the release of substance P is less than that of capsaicin. These results suggest that the release of substance P is partially involved in the mechanism of analgesic action of DA-50l8.

• Korean Journal of Pharmacognosy
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• v.16 no.4
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• pp.199-205
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• 1985

In order to investigate experimentally the clinical effects of Soeuminsohapwon that was prescribed to cure cerebral hemorrhage, palpitation etc, the author tested various activities of extract from the Soeuminsohapwhangwon by the method prescribed in the experimental part. The results of the studies were summarized as follows: Suppressive action was not shown on the convulsion induced by strychnine, but significant effect was noted on the convulsion induced by picrotoxin and caffeine. In acetic acid method, analgesic effect was noted. A prolongation of anesthetic time by pentobarbital sodium and antipyretic effect was observed. Relaxing action was noted on the ileum of mice, also same effect was recognized on contraction of the ileum due to acetylcholine, barium chloride and histamine. The expansion of blood vessels by relaxation of smooth muscle and hypotensive action were noted. According to the above results, effects based on oriental medical references were approximate to the actual experimental results.

• Natural Product Sciences
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• v.23 no.2
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• pp.108-112
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• 2017

Anti-inflammatory, anti-arthritic and analgesic activity of each herbal extract, which is extracted from Bacopa monnieriis, Cassia fistula and Phyllanthus polyphyllus, respectively. The treatment of herbal extract exhibited anti-inflammatory effect as a dose-dependent manner, from 1.25 mg/kg to 12.5 mg/kg, in acute inflammatory models (carrageen and egg-albumin induced rat hind paw edema). It also elicited significant anti-inflammatory activity in chronic inflammatory models (cotton pellet granuloma and Freund's adjuvant induced polyarthritis in rat). In cotton pellet granuloma test, the extract exhibited the inhibitory effect of 23 and 57% at the dose of 6.25 and 12.5 mg/kg, respectively. In Freund's adjuvant induced model, the treatment of the extract of 1.25, 6.25 and 12.5 mg/kg showed the inhibitory effect of 23, 56 and 66% at 8 days, respectively. In the acetic acid-induced model, the extract significantly reduced abdominal writhing in mice when compared to the control group, reducing the mean number of writhing from $41{\pm}2$ in the control group to $17{\pm}3$ and $15{\pm}2$ at the dose of 6.25 and 12.5 mg/kg. From these experiments, the extract, which was extracted from the combination of Bacopa monnieriis, Cassia fistula and Phyllanthus polyphyllus, (w/w/w = 1/2/1) is surprisingly found a significant analgesic and anti-inflammatory activity.

• The Korean Journal of Pain
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• v.8 no.1
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• pp.43-50
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• 1995

The purpose of this study was to compare postoperative analgesic effect according to intravenous doses of ketorolac. The ninety-eight adult patients, scheduled for elective surgery under general anesthesia, were randomly assigned to receive saline or one of the five doses of ketorolac (10, 15, 30, 45, 60mg). After recoverg from anesthesia, saline or ketorolac was injected intravenously, and the visual analogue score, sedation secore, mean blood pressure, heart rate, and the incidence of nausea and vomiting were measured 30 minutes, 1 hour and 2 hours the injection. Saline or 10 mg of ketorolac had no postanalgesic effect. Above 15 mg of ketorolac had analgesic effect, but this analgesic effect was not increased with increasing doses of ketorolac (30, 45, 60 mg). Any side effects (nausea, vomiting, excessive sedation, cardiopulmonary depression, and renal and hematologic adverse events) was not observed associated with ketorolac administration. These results suggested that 15 mg of ketorolac is the most reliable dose for postoperative anlgesia in intravenous administration.

• Toxicological Research
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• v.11 no.1
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• pp.63-68
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• 1995

N-methyl-D-aspartate(NMDA) receptor has been well known as an important mediator of several forms of neural and behavioral plasticity. But different results were reported about the effect of MK-801 or dextromethorphan on opioid dependence. The present studies examined whether NMDA receptor antagonists can alter the opioid dependence and tolerance in rodents. Naloxone precipitated withdrawal symptoms and changes of locomotor activities were observed in MK-801 or dextromethorphan pretreated morphine-dependent rats. Tail-flick assay was used for morphine analgesia and tolerance was found after 4 day's consecutive injections (10 mg/kg, s.c., twice/day) of morphine in mice. Locomotor activity was increased and the withdrawal symptoms were decreased by the pretreatment of MK-801 in morphine-dependent rats. But 0.3 mg/kg i.p. of MK-801 intensified the body weight loss and produced severe ataxia and rotation although some withdrawal signs were attenuated. Morphine induced analgesic tolerance was inhibited by the pretreatment of MK-801 and dextromethorphan. Dextromethorphan was more potent than MK-801 in inhibiting the development of the analgesic tolerance in mice. These results suggest that NMDA system may be involved in opioid withdrawal and analgesic tolerance but appropriate caution should be requested when MK-801 is used in combination with opioid because of untoward neurologic signs.

• Herbal Formula Science
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• v.11 no.1
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• pp.161-170
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• 2003

This study was designed to elucidate the analgesic effects of Jakyakgamchotang and Radix paeinia, Radix Glycyrrhiziae which are the component of Jakyakgamchotang in mice. The analgesic effects were measured by the Whittle's method and hot plate method. The results were as follows ; After the administration of Jakyakgamchotang extrace, the frequency of writhing syndrome was significantly inhibited. After the administration of Radix paeinia extract, the frequency of writhing syndrome was significantly inhibited. After the administration of Radix Glycyrrhiziae extract, the frequency of writhing syndrome was significantly inhibited. After the administration of Jakyakgamchotang extrace, paw licking time and escape time were significantly prolonged. After the administration of Radix paeinia extract, paw licking time was significantly prolonged. After the administration of Radix Glycyrrhiziae extract, paw licking time was significantly prolonged. It is concluded that the analgesic effects of Jakyakgamchotang were found to be more effective than Radix paeinia and Radix Glycyrrhiziae.

• YAKHAK HOEJI
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• v.36 no.5
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• pp.474-480
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• 1992

Astilbes rhizoma has been used for headache, arthralgia, chronic bronchitis and stomachalgia in traditional chinese medicine. The analgesic activities and their components of Astilbe chinensis var. davidii Rhizomes were evaluated. The ether and ethylacetate fractions of 70% EtOH extract showed considerable analgesic activities by acetic acid induced writhing method. Compound $1{\sim}5$ were isolated from ethylacetate fraction and identified as gallic acid, (+)-catechin, (+)-gallocatechin, bergenin and 11-O-galloylbergenin on the basis of spectroscopic methods. Among them (+)-gallocatechin showed stronger analgesic activity than that of other compounds.

• The Korean Journal of Pain
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• v.27 no.2
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• pp.103-111
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• 2014

Nefopam (NFP) is a non-opioid, non-steroidal, centrally acting analgesic drug that is derivative of the nonsedative benzoxazocine, developed and known in 1960s as fenazocine. Although the mechanisms of analgesic action of NFP are not well understood, they are similar to those of triple neurotransmitter (serotonin, norepinephrine, and dopamine) reuptake inhibitors and anticonvulsants. It has been used mainly as an analgesic drug for nociceptive pain, as well as a treatment for the prevention of postoperative shivering and hiccups. Based on NFP's mechanisms of analgesic action, it is more suitable for the treatment of neuropathic pain. Intravenous administration of NFP should be given in single doses of 20 mg slowly over 15-20 min or with continuous infusion of 60-120 mg/d to minimize adverse effects, such as nausea, cold sweating, dizziness, tachycardia, or drowsiness. The usual dose of oral administration is three to six times per day totaling 90-180 mg. The ceiling effect of its analgesia is uncertain depending on the mechanism of pain relief. In conclusion, the recently discovered dual analgesic mechanisms of action, namely, a) descending pain modulation by triple neurotransmitter reuptake inhibition similar to antidepressants, and b) inhibition of long-term potentiation mediated by NMDA from the inhibition of calcium influx like gabapentinoid anticonvulsants or blockade of voltage-sensitive sodium channels like carbamazepine, enable NFP to be used as a therapeutic agent to treat neuropathic pain.

• The Korean Journal of Pain
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• v.18 no.1
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• pp.10-14
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• 2005

Background: Previous studies have suggested synergistic analgesic drug interactions between NSAIDs and opioids in neuropathic and inflammatory pain models. The aim of this study was to investigate the analgesic drug interaction between intraperitoneal (IP) ketorolac and morphine in radiant thermal stimulation rat. Methods: Initially, we assessed the withdrawal latency time of the hindpaw to radiant thermal stimulation every 15 min for 1 hour and every 30 min for next 1 hour after IP normal saline 5 ml (control group). The latency time was changed into percent maximal possible effect (%MPE). Next, IP dose response curves were established for the %MPE of morphine (0.3, 1, 3, 10 mg/kg) and ketorolac (3, 10, 30 mg/kg) to obtain the $ED_{50}$ for each agent. And we confirmed that the IP morphine effect was induced by opioid receptor through IP morphine followed by IP naloxone. At last, we injected three doses of IP ketorolac (3, 10, 30 mg/kg) mixed with one dose of morphine (2 mg/kg) for fixed dose analysis. Results: IP morphine delayed the paw withdrawal latency time dose dependently, but not ketorolac. $ED_{50}$ of IP morphine was 2.1 mg/kg. And the IP morphine effect was reversed to control level by IP naloxone. IP ketorolac + morphine combination showed no further additional effects on paw withdrawal latency time over morphine only group. Conclusions: IP ketorolac did not produce antinociceptive effect during radiant thermal stimulation. There was neither additional nor synergistic analgesic interaction between IP morphine and ketorolac in thermal stimulation rat.

• Advances in Traditional Medicine
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• v.8 no.2
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• pp.196-203
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• 2008

The methanol extract of the root of Artanema sesamoides Family Scrophuilariaceae (MEAS) was investigated for possible analgesic and anti-inflammatory effects in animals. Three models were used to study the extract effects on nociception, which were acetic acid-induced writhing response, hot-plate method and the tail flick test in mice. The antiinflammatory effects were evaluated using carrageenan, dextran, histamine and serotonin induced rat paw oedema (acute) and cotton pellet induced granuloma (chronic) models in rats. Results of the study revealed that the extract exhibited significant (P < 0.001) analgesic effect at a dose of 50, 100 and 200 mg/kg b.w p.o in mice in all the models. In acute model, the MEAS also exhibited significant (P < 0.001) antiinflammatory effect in all the above mentioned doses. In chronic model (cotton pellet induced granuloma) the MEAS 200 mg/kg and indomethacin 10 mg/kg showed that inhibition of granuloma formation 25.0% and 47.7% respectively (P < 0.001). The MEAS and indomethacin were effectively preventing the transudation of the fluid. Thus, the present study revealed that the methanol extract of the root of Artanema sesamoides exhibited significant analgesic and antiinflammatory activity.