• Journal of Yeungnam Medical Science
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• v.10 no.2
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• pp.445-450
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• 1993

Recent studies have shown that opiods can produce potent antinociceptive effects by interacting with opioid receptors in peripheral tissues. This study sougt to compare the effects of morphine with those of bupivacaine administered intraarticularly upon pain after arthroscopic knee surgery. In a ramdomized manner, 60 healthy patients received either morphine(3 mg in 20 ml NaCl ; n=20), bupivacaine(20 ml, 0.25% ; n=20) intraarticularly at the completion of surgery, and others were not administered(n=20) under general anesthesia after 1, 2, 4, 6, 12 and 24h of postoperative day, pain was assessed by a visual analogue pain scales, time to first analgesic use were recorded. Pain scores were significantly greater in the morphine group than two groups at 1h. From 4th until the end of the study period, pain scores were significantly greater in the bupivacaine group than in the other two group. Anagesic requirements were significantly greater in the morphine group than two groups at 1h but were significantly greater in the bupivacaine group than in the other groups throughout the remainder of the study period. The results suggest that intraarticular morphine produces an analgesic effect of delayed onset but of remarkably long duration.

• YAKHAK HOEJI
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• v.49 no.5
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• pp.370-374
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• 2005

Lactoferrin is a multifunctional protein that is found in milk, neutrophils, and other biological fluids, and its receptors have also been identified in the central nervous system. Recently, it was reported that bovine milk-derived lacto­ferrin (BLF) produced analgesia via a $\mu$-opioid receptor-mediated response in the spinal cord. However the precise mech­anism of this analgesic effect is remains unclear. In Randall-Selitto paw pressure study, each single administration of morphine (10 mg/kg) and BLF (50, 100 and 200 mg/kg) induced analgesia, however, NMDA receptor antagonist MK-801 (0.1, 0.2 and 0.3 mg/kg), inhibited analgesia induced by BLF (100 mg/kg). Intracerebroventricular infusion (I.C.V.) of N­methyl-D-aspartic acid (NMDA) ($0.3\;{\mu}g/8.0\;{\mu}l/hr/day$), as a NMDA receptor agonist, reversed inhibition of MK-801 (0.3 mg/kg) on analgesia induced by BLF (100 mg/kg). These results suggest that BLF have analgesic effect, through NMDA recep­tor activation.

• The Journal of Korean Medicine
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• v.25 no.3
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• pp.67-77
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• 2004

Objectives : Many studies have reported that acupuncture analgesia was mediated through the activation of peripheral and central opioid receptors. However, there has been little electrophysiological study on the adrenergic mechanism of acupuncture analgesia in chronic inflammatory and neuropathic pain. The present study was undertaken to elucidate the role of adrenoceptors in the production of acupuncture analgesia in the chronic pain model. Methods : In the rat with chronic inflammation and nerve injury, dorsal horn cell (DHC) responses to afferent C fiber stimulation were used as a pain index and changes in electroacupuncture (EA) analgesia were recorded before and after intravenous administration of selective adrenoceptor antagonists. EA stimulations (2Hz, 0.5msec, 3mA) were applied to the contralateral Zusanli point for 30 min. Results : EA stimulation induced long-lasting inhibition of DHC responses in the rat with chronic inflammation and nerve injury. In both models of inflammation and neuropathic pain, α-adrenoceptor antagonist (phentolamine) significantly attenuated an inhibitory effect of EA on DHC responses. Selective α2-adrenoceptor antagonist (yohimbine) also had a similar suppressive action on DHC responses to that of phentolamine. However, β-adrenoceptor antagonist (propranolol) did not have any inhibitory effect on DHC responses in either model of chronic pain. Conclusions : These experimental findings suggest that in rats with chronic pain, EA stimulation with low frequency and high intensity produced an analgesic effect which was mediated through an activation of α2-adrenoceptors.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.5
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• pp.285-289
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• 2010

In the present study, the antinociceptive profiles of $Campanula$ $punctata$ extract were examined in ICR mice. The $Campanula$ $punctata$ contain a large dose of saponin. $Campanula$ $punctata$ extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, $Campanula$ $punctata$ extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P ($0.7{\mu}g$) was diminished by $Campanula$ $punctata$ extract. Intraperitoneal (i.p.) pretreatment with yohimbine (${\alpha}_2$-adrenergic receptor antagonist) attenuated antinociceptive effect induced by $Campanula$ $punctata$ extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by $Campanula$ $punctata$ extract in the writhing test. Our results suggest that $Campanula$ $punctata$ extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of $Campanula$ $punctata$ extract may be mediated by ${\alpha}_2$-adrenergic receptor, but not opioidergic and serotonergic receptors.

• Journal of The Korean Society of Clinical Toxicology
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• v.7 no.2
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• pp.172-175
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• 2009

Zipeprol dihydrochloride is a non-opioid mucolytic, antitussive agent and it is frequently prescribed for respiratory symptoms such as cough and sputum. The main pharmacologic mechanisms of zipeprol are inhibition of superior laryngeal nerve stimulation and direct antagonism for stimulation of the bronchial receptors, which might have an effect for the drug's mucolytic action. Many cases of drug abuse with zipeprol have occurred world-wide due to the hallucinogenic effect of the drug. In Korea, zipeprol was reported to be the most commonly abused drug among young people for the 1990s. Zipeprol associated death was first reported since 1991 and 69 cases of death related to zipeprol abuse were further reported during 8 years (between 1991 and 1998). In addition to the hallucinogenic effect, dyspnea, extrapyramidal symptoms, seizure, cerebral edema have been reported as the signs and symptoms of toxic zipeprol overdose. However, zipeprol abuse is not common for old age people and non drug abusers. We report here on a fatal case of acute zipeprol poisoning in an eighty five year old drug addicted woman.

• Journal of Acupuncture Research
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• v.27 no.5
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• pp.13-24
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• 2010

Objectives : This study was designed to investigate the effects of bee venom acupuncture at Shinsu($BL_{23}$) and Daejangsu($BL_{25}$) on neuropathic pain induced by tibial and sural nerve injury in rats. Methods : Neuropathic pain model was made by partial resection of tibial and sural nerve. Three weeks after the neuropathic surgery, bee venom acupuncture was firstly injected at $BL_{23}$ and $BL_{25}$, then we measured withdrawal responses induced by von Frey filament and acetone stimulation. Bee venom acupunctures were injected 6times on every 2days. Measurement of withdrawal responses were conducted on the same days. After bee venom acupuncture injection, expression levels of c-Fos, nocieptin and KOR-3 were observed through using immunohistochemistry. Results : In this experiment, bee venom acupunctures at $BL_{23}$ and $BL_{25}$ decreased levels of withdrawal responses induced by von Frey filament and acetone stimulation respectively. In addtion, expression levels of c-Fos, nociceptin and KOR-3 in central gray part of brain in rats were decreased by bee venom acupuncture. Conclusions : These results imply that bee venom acupuncture was useful to treat patients with neuropathic pain, and related mechanisms were involved in opioid and their receptors such as nociceptin and KOR-3.

• Journal of Pharmacopuncture
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• v.12 no.2
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• pp.67-75
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• 2009

Objectives : This study was performed to developing orally administered analgesics and locally injected pharmacopuncture analgesics like opioids. Methods : Literary investigation on the origin of poppy (Papaver somniferum L) and other narcotics was conducted to examine the potential of developing orally administered analgesics and locally injected pharmacopuncture analgesics. Opium is a gum-like mass derived from air-dried white fluid of immature fruit of the poppy. Opium contains approximately 20 types of alkaloids including morphine, codeine, thebaine, papaverine and others. Natural opioids and synthetic alkaloid derivatives are the constituents of opioid analgesics and their effects and side-effects depend on the peculiarities of receptors. An extreme caution is required in the selection of proper dosage, proper analgesic types, and indications for successful pain management. Results and Discussion : With the enactment of "Narcotic control protocol", herbs such as cannibis and poppy are no longer available for use by Korean medicine doctors, and these doctors are faced with difficulty in managing severe pain in the clinical environment. A systematic consideration is inevitable for overcoming the limitation on these analgesics.

• Proceedings of the PSK Conference
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• 2000.04a
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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 Pharmacology
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• v.28 no.1
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• pp.61-74
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• 1992

Influence of the blockade of the three major pressor systems-sympathetic nervous system (SNS), renin-angiotensin system (RAS) and vasopressin system-on the pressor responsiveness to norepinephrine (NE), angiotensin II (AII), and vasopressin (VP) as well as on basal blood pressure (BP) levels was investigated in urethane-anesthetized rabbits. To block the SNS and RAS, chlorisondamine (CS) and pirenzepine (PZ), sympathetic ganglionic blockers, and enalapril (ENAL), an inhibitor of angiotensin converting enzyme, respectively were used. And for suppressing the VP system bremazocine (BREM), a kappa opiate receptor agonist shown to suppress plasma levels of VP, was employed. Each of CS (0.4 mg/kg), ENAL (2 mg/kg), and BREM (0.25 mg/kg) produced almost same levels of steady hypotensive state. The hypotensive effect of BREM was significantly attenuated by desmopressin, a synthetic VP-like analogue, suggesting the hypotension being at least in part due to suppression of plasma levels of VP. CS, ENAL and BREM elicited further fall of the BP which had been lowered by ENAL or BREM, CS or BREM, and CS or ENAL, respectively. The hypotension produced by both CS and PZ together with either of ENAL or BREM was more marked than that produced by the three drugs other than CS. CS potentiated the pressor response not only to NE but to AII and VP. The pressor effect of AII was increased by ENAL and BREM, too. The pressor response to VP was also enhanced by BREM. Blockade of ${\alpha}-adrenergic$ receptors with phentolamine or phenoxybenzamine potentiated the pressor response to AII and that to VP. The results on basal BP levels indicate that the three major pressor systems are all participating in control of BP, but SNS has the greatest potential for supporting BP. The finding that blockade of one of the pressor systems induced enhanced pressor responsiveness to the pressor hormone of that particular system as well as to the pressor hormone(s) of the other systems(s) provides evidence for important interactions among the three major pressor systems.