• Journal of Veterinary Clinics
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• v.24 no.4
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• pp.499-502
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• 2007

The study was performed to assess the antinociceptive efficacy of Korean bee venom(BV) in the rat formalin test. Korean BV was collected using BV collector devices in which an electrical impulse is used to stimulate the worker bee(Apis mellifera L.) to sting and release venom. After collection, whole Korean BV was evaporated until dry using BV collector. Experiments were performed on male Sprague-Dawley rats(weighing 260-270, 6 weeks old). Rats divided into 4 groups, each comprising 8 rats. BV was diluted and amounts of 6 mg/kg body weight(BW), 0.6 mg/kg BW and 0.06 mg/kg BW were tested. BV was subcutaneously injected to produce an antinociceptive effect and the antinociceptive efficacy was evaluated using a rat formalin test. BV was subcutaneously injected into an acupoint(Zusanli, ST36) at 15 min prior to 1% formalin($50{\mu}l$) injection. The antinociceptive effect observed during 60 min following formalin administration. BV produced antinociceptive efficacy from 10 to 60 min after formalin injection. The antinociceptive efficacy of Korean BV showed a dose-dependent response. These results suggest that Korean BV may be a suitable and preferred choice for antinociceptive efficacy in pain management.

• Journal of Veterinary Clinics
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• v.27 no.6
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• pp.663-667
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• 2010

Experiments were undertaken to assess the antinociceptive effect of bee venom (BV) in rodent animal models. Comparison of antinociceptive efficacy between Korean BV and commercially available American BV was the primary interest of the study. Korean BV was collected using BV collector devices in which an electrical impulse is used to stimulate the worker bee (Apis mellfera L.) to sting and release venom. After collection, whole BV was evaporated until dry using the BV collector. Commercially available dried American BV was purchased from Sigma Company in USA. Korean and American sourced BVs were diluted and amounts of 6 mg/kg body weight (BW), 0.6 mg/kg BW and 0.06 mg/kg BW were tested. BV was subcutaneously injected to produce an antinociceptive effect and the antinociceptive efficacy was evaluated using a writhing test in mice and a formalin test in rats. The antinociceptive effects of the two BVs tested were similar in mice for visceral pain and showed a dose-dependent response. The antinociceptive effect of Korean BV was not significantly different compare to American BV. These results suggest that Korean BV may be used to achieve an antinociceptive effect for use in medical therapies.

• Journal of Veterinary Clinics
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• v.24 no.3
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• pp.320-324
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• 2007

This study was undertaken to assess the antinociceptive effect of Korean bee venom (BV) in mice. Korean BV was collected using BV collector devices in which an electrical impulse is used to stimulate the worker bee (Apis mellifera L.) to sting and release venom. After collection, whole BV was evaporated until dry using the BV collector. Experiments were performed on male ICR mice (weighing $30{\sim}35g$, 6 weeks old). Mice were divided into 4 groups, each comprising 8 mice. BV was diluted and amounts of 6 mg/kg body weight (BW), 0.6 mg/kg BW and 0.06 mg/kg BW were tested. BV was subcutaneously injected to produce an antinociceptive effect and the antinociceptive efficacy was evaluated using a writhing test in mice. Intraperitoneal injection of acetic acid produced a tonic pain behavior, first observed at 3 to 9 min post-injection. This writhing response peaked at 20 min post-acetic acid injection, and then declined until it was undetectable at 60 min post-injection. The time elapse between the administration of acetic acid and the first observed pain behaviors indicated a dose-dependent suppressive effect. These results suggest that Korean BV may be used to achieve an antinociceptive effect for use in medical therapies.

• Biomolecules & Therapeutics
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• v.5 no.1
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• pp.67-73
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• 1997

Analgesic effect of DA-5018, a new capsaicin derivative, was evaluated in various rat models of experimentally induced acute pain. DA-5018(0.2∼10.0 mg/kg, p.o.) prevented the writhing syndromes induced by acetic acid or phenol-p-benzoquinone(PBQ). It increased the pain threshold of inflamed paw when tested by the Randall-Selitto method at the dose of 2.0∼20.0 mg/kg by oral administration. And also it showed antinociceptive activities in tail-pinch(1.0∼20.0 mg/kg, p.o.) and tail-flick test(5.0∼50.0 mg/kg, p.o.). the potency and efficacy of DA-5018 were comparable to morphine · HCI in all the models mentioned above. Acetaminophen exhibited the inhibition of acetic acid-induced writhing syndromes and also analgesic activity in Randall-Selitto test, but it showed the limited efficacy in tail-pinch and tail-flick test. These results mean that DA-5018 has a broader analgesic activity profile than acetaminophen. And we found out that the analgesic activity of DA-5018 was 100 times more potent when administered centrally than administered orally in tail-flick test. These results suggest that DA-5018 has an orally active analgesic activity, and central nervous system may be involved in the action of DA-5018.

• Proceedings of the Ginseng society Conference
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• 1998.06a
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• pp.31-39
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• 1998

We have investigated the antinociceptive efficacy of ginseng saponins in mice using l% formalin, which induce two phases of pain (acute and tonic pains) and is known to induce a clinically related pain. Ginseng total saponins (GTS) relieved both phases of pain with EDso of 162 mghg for acute and 92 mg/kg for tonic pain, respectively. Both protopanaxadiol (PD) and protopanaxatriol (PT) saponins did not attenuated acute phase of pain but relieved tonic phase of pain with EDso of 45 mg/kg for PD saponins and 105 mghg for PT saponins, respectively. Moreover, ginsenoside Rc, Rd, and Re among representative ginsenosides such as Rbl, Rc, Rd, Re and Rgl relieved slightly but significantly acute phase of pain and strongly attenuated tonic phase of pain but Rf relieved only tonic phase of pain. However, PD and PT saponins, and the individual ginsenosides tested except GTS did not greatly attenuate thermal noxious pain (tail-flick test). These results suggest that single ginsenoside or mixture of various ginsenosides mainly induce differential antinociception in mice.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.2
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• pp.125-130
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• 2015

Cholecystokinin is known to be involved in the modulation of nociception and to reduce the efficacy of morphine analgesia. This study investigated the effects of intrathecal administration of morphine and the cholecystokinin type B antagonist CI-988 on below-level neuropathic pain after spinal cord injury in rats. We also examined the interaction of morphine and CI-988 in the antinociceptive effect. Both morphine and CI-988 given individually increased the paw withdrawal threshold to mechanical stimulation in a dose-dependent manner. The combination of ineffective doses of intrathecally administered CI-988 and morphine produced significant analgesic effects and the combination of effective doses resulted in analgesic effects that were greater than the sum of the individual effects of each drug. Thus, morphine showed a synergistic interaction with CI-988 for analgesia of central neuropathic pain.

• The Korean Journal of Pain
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• v.23 no.3
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• pp.172-178
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• 2010

Background: Tumor necrosis factor-alpha and other proinflammatory cytokines are becoming well recognized as key mediators in the pathogenesis of many types of neuropathic pain. Thalidomide has profound immunomodulatory actions in addition to their originally intended pharmacological actions. There has been debate on the analgesic efficacy of opioids in neuropathic pain. The aim of this study was to investigate the effect of thalidomide and morphine on a spinal nerve ligation model in rats. Methods: Male Sprague-Dawley rats weighing 100-120 g were used. Lumbar (L) 5 and 6 spinal nerve ligations were performed to induce neuropathic pain. For assessment of mechanical allodynia, mechanical stimulus using von Frey filament was applied to the paw to measure withdrawal threshold. The effects of intraperitoneal thalidomide (6.25, 12.5, 25 and 50 mg/kg, respectively) and morphine (3 and 10 mg/kg, respectively) were examined on a withdrawal threshold evoked by spinal nerve ligation. Results: After L5 and 6 spinal nerve ligation, paw withdrawal thresholds on the ipsilateral side were significantly decreased compared with pre-operative baseline and with those in the sham-operated group. Intraperitoneal thalidomide and morphine significantly increased the paw withdrawal threshold compared to controls and produced dose-responsiveness. Conclusions: Systemic thalidomide and morphine have antiallodynic effect on neuropathic pain induced by spinal nerve ligation in rat. These results suggest that morphine and thalidomide may be alternative therapeutic approaches for neuropathic pain.

• The Korean Journal of Pain
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• v.25 no.1
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• pp.1-6
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• 2012

Background: Curcumin has been reported to have anti-inflammatory, antioxidant, antiviral, antifungal, antitumor, and antinociceptive activity when administered systemically. We investigated the analgesic efficacy of intrathecal curcumin in a rat model of inflammatory pain. Methods: Male Sprague Dawley rats were prepared for intrathecal catheterization. Pain was evoked by injection of formalin solution (5%, $50{\mu}l$) into the hind paw. Curcumin doses of 62.5, 125, 250, and $500{\mu}g$were delivered through an intrathecal catheter to examine the flinching responses. The $ED_{50}$ values (half-maximal effective dose) with 95% confidence intervals of curcumin for both phases of the formalin test were calculated from the dose-response lines fitted by least-squares linear regression on a log scale. Results: In rats with intrathecal administration of curcumin, the flinching responses were significantly decreased in both phases. The slope of the regression line was significantly different from zero only in phase 2, and the $ED_{50}$ value (95% confidence interval) of curcumin was $511.4{\mu}g$ (23.5-1126.5). There was no apparent abnormal behavior following the administration of curcumin. Conclusions: Intrathecal administration of curcumin decreased inflammatory pain in rats, and further investigation to elucidate the precise mechanism of spinal action of curcumin is warranted.

• Journal of Korean Neurosurgical Society
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• v.30 no.4
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• pp.417-424
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• 2001

Objective : Adrenal medullary chromaffin cells are known to release analgesic substances such as opioides and catecholamines. Transplantation of them is a novel method that challenges current approaches in treating chronic pain. The transplantation of xenogeneic chromaffin cells into the central nervous system(CNS) supply antinociception in animals. In this study, we investigated the analgesic effects of rat adrenal medullary chromaffin cells transplanted into the CNS of the mouse. To study the antinociceptive efficacy of transplanted chromaffin cells, the survival of rat adrenal medullary chromaffin cells transplanted into the CNS of mouse was determined. Methods : The adrenal medullary chromaffin cells isolated from rat were transplanted into the striatum of mouse. These cells were confirmed of the release of Met-enkephalin and Leu-enkephalin by HPLC, and immunoblots for tyrosine hydroxylase(TH). Two weeks after transplantation, we performed immunohistochemistry for TH to determine the survival of implanted cells and assessed pain sensitivity at the same time. Results : The isolated rat adrenal medullary chromaffin cells were positive for anti-TH antibody and released Met-enkephalin and Leu-enkephalin more than rat endothelial cells. Transplanted rat chromaffin cells were stained with anti-TH antibody in striatum of mouse after 2 weeks. Pain sensitivity was reduced on the chromaffin cell-transplanted mouse compared to endothelial cell-transplanted mouse by the hot plate test. Conclusion : These results suggest that the rat chromaffin cells were suitably transplanted into the CNS of mouse. This approach could be used as a therapy for reducing of chronic pain induced by cancer or neuronal injury.

• Clinical and Experimental Pediatrics
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• v.51 no.5
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• pp.481-486
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• 2008

Purpose : The aims of this study were to test the efficacy of vapocoolant spray to decrease the symptoms associated with pain in newborns undergoing heel stick and intramuscular injection and compare the pain relief effect of oral glucose. Methods : Randomized, controlled study including sixty newborns undergoing heel stick and intramuscular injection. Group 1 was heelsticked, Group 2 was intramuscular injected, Group A did not recieve any treatment, Group B recieved 30% glucose solution orally, Group C was applied vapocoolant spray symptoms and signs associated with pain at heel stick and intramuscular injection were measured with the premature Infant Pain Profile (PIPP) scale. Results : There was no significant difference in the PIPP score between intramuscular injected group control and heel stick group control (P=0.07). The mean PIPP score of Group 1A (control) $10.6{\pm}2.4$, Group 1B $5.5{\pm}2.0$, Group 1C $5.2{\pm}1.8$. The mean PIPP score 1B and 1C were significantly lower than control (1B P<0.001, 1C P<0.001). The mean PIPP score of Group 2A (control) $12.5{\pm}1.4$, Group 2B $7.0{\pm}1.7$, Group 2C $6.4{\pm}1.6$. The mean PIPP score 2B and 2C were significantly lower than control (2B P<0.001, 2C P<0.001). Conclusion : The antinociceptive effect of vapocoolant sparay is as effective as 30% oral glucose solution for pain control. So this study support the use of vapocoolant spray for reducing pain during painful procedure in the neonatal intensive care units.