• Journal of Ginseng Research
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• v.23 no.4
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• pp.239-246
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• 1999

The analgesic effect of ginsenosides or morphine was determined following intrathecal (i.t.) administration in rat tail-flick test. The effects of intrathecal co-administration of ginsenosides with morphine on the development of opioid tolerance and dependence were also examined using rat tail-flick test and naloxone-pre-cipitated withdrawal, respectively. Administration of ginsenosides (i.t.) produced a weak antinociception in a dose-dependent manner. Administration of morphine (i.t.) also produced antinociception in a dose-dependent manner. The $ED_50$ was $1.20\;{\mu}g\;(1.14\~1.29\;{\mu}g)$. However, the acute co-administration of $200{\mu}g$ ginsenosides with 0.1-1.0${\mu}g$ morphine did not show additive effect on morphine induced analgesia in rat tail-flick test. I.t. co-administration of 200 ${\mu}g$ ginsenosides with 10 ${\mu}g$ morphine for 7 days inhibited development of tolerance induced by 10 ${\mu}g$ morphine in rat tail-flick test, although i.t. co-administration of 50 or 100 ${\mu}g$ ginsenosides with morphine was without effect. I.t. co-administration of 200 ${\mu}g$ ginsenosides for 7 days also partially attenuated the development of morphine dependence as assessed by naloxone-precipitated withdrawal. In conclusion, these results suggest that i.t. administered ginsenosides produce a weak antinociception in rat tail-flick test and also prevent opioid tolerance and attenuate opioid dependence in chronic treatment with morphine at the spinal sites.

• Journal of Hospice and Palliative Care
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• v.11 no.3
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• pp.136-139
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• 2008

Purpose: Epidural morphine infusion has been used to control pain in cancer patients whose cancer pain can not be controlled high dose intravenous morphine injection. To study the effectiveness and side effects of epidural morphine for the treatment of cancer pain in terminal patients at Hospice Ward, we evaluated the change in morphine equivalent daily dose for effectiveness and complications of epidural morphine infusion. Methods: We retrospectively analyzed 24 terminal cancer patients who were treated with continuous epidural morphine between 2001 and 2004 at Hospice Ward of St. Vincent's Hospital. Results: The median of baseline morphine equivalent daily dose was 615 mg, whereas the median dose of initial epidural morphine was 16 mg. The median of morphine daily equivalent daily dose dropped from 615 mg to 274 mg in one week after epidural morphine infusion therapy (P-value=0.000). The median survival from the time of the first catheter insertion was 35 days. In 6 patients, the catheter was removed due to complications, however the catheter was reinserted in 3 patients. Conclusion: Cancer pain management by epidural morphine infusion is very effective method with low rate of severe complication.

• Journal of Acupuncture Research
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• v.27 no.4
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• pp.55-65
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• 2010

목적 : 기존 연구에서 신문혈 자침은 알코올 및 코카인을 자가섭취하는 동물 모델에서 효과적이라는 점이 밝혀졌으며, 또한 모르핀 자가섭취를 억제할 수 있음이 밝혀졌다. 이러한 결과를 바탕으로 본 연구에서는 자침의 효과가 얼마나 지속될 수 있는지 알아보았다. 재료 및 방법 : 체중 270~300g의 수컷 SD계 흰쥐를 이용하였다. 먹이섭취 훈련을 통과한 후 오른쪽 경정맥에 관을 삽입하는 수술을 거쳐, 0.1mg/kg의 모르핀을 매일 1시간, 총 3주 동안 자가섭취 하도록 하였다. 모르핀을 일정하게 섭취한 동물에게는 다음날 침술을 시행하였다. 두 번째 실험에서는 GABAA 및 GABAB 길항제를 자침 30분 전에 투여하여 침술의 효능과 GABA 수용체계 사이의 관계를 검증하였다. 결과 : 모르핀 자가섭취를 억제하는 신문혈 자침의 효과는 매일 비슷하게 나타나지 않았으며, 4일째에는 유의한 효과가 없는 것으로 나타났다. 그러나 5일째와 6일째에는 다시 유의한 효과가 나타나 뒤집어진 U 자형 곡선을 나타내었다. 또한 GABA 수용체의 길항제들은 자침의 효과가 유의하게 나타났을 때 이를 차단하는 결과를 보였다. 결론 : 모르핀 중독 치료에서 침술의 효과는 항상 비슷하게 발휘되는 것이 아니므로 침 치료는 적어도 1주일에 2회 이상 받을 필요가 있다. 아울러 보다 심도 있는 연구를 위하여 뇌신경 체계에 대한 연구가 이루어질 필요가 있는 것으로 사료된다.

• YAKHAK HOEJI
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• v.29 no.4
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• pp.188-192
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• 1985

Protopanaxadiol (PD) fraction and protopanaxatriol (PT) fraction were separated from thebutanol fraction of panax ginseng roots. Each group of mice was injected with morphine hydrochloride (40 mg/kg s.c.) three times at 8 hr intervals for a period of 6 days. PD fraction and PT fraction were injected (25, 100 mg/kg i.p.) to mice 1 hr prior to the third morphine injection daily. Inhibition of morphine tolerance was evidenced by the increase in analgesic response to morphine hydrochloride (10mg/ kg i.p.) as estimated by the tail flick method. Inhibition of morphine tolerance by PT fraction was effective but there was no remarkable difference in inhibition of tolerance development between control group andPD fraction group.

• Korean Journal of Acupuncture
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• v.29 no.2
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• pp.179-187
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• 2012

Objectives : Since acupuncture was accepted as an useful therapy for the drug addiction, a lot of studies about acupuncture have been carried out. This study was performed to review the articles about morphine addiction which used acupuncture as a treatment and to interpret the use of acupoints from the viewpoint of Six-meridian (Yuk Gyeong, three yin and three yang) theory. Methods : The authors searched 255 articles in PubMed with the key word of "morphine, acupuncture" and 629 articles in KISS (Koreanstudies Information Service System) with the key word of "morphine". The articles written in English only were included. The articles related with morphine (abuse, dependence, sensitization, addiction, intake, withdrawal sign, withdrawal syndrome, reinstatement, craving) only were included. The articles which used manual- or electro-acupuncture only were included and auricular acupuncture was excluded. Both of clinical and experimental study were reivewed. Results : The most frequently used acupoint was ST36-SP6 (electroacupuncture), and the second was HT7. LI4 was the third, and BL23 and PC6 were also used. Conclusions : The acupoints used in the morphine study seem to influence the brain through diverse mechanisms and it is thought that control of the reaction against stress appears to be related with these mechanisms.

• The Korean Journal of Pain
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• v.14 no.2
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• pp.225-230
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• 2001

Background: Opioids such as morphine are widely used in the treatment for pain, but chronic treatment with morphine can be complicated by the development of tolerance. The mechnisms of tolerance were still not completely understood, but recently it has been reported that NOS inhibitors can prevent development of morphine tolerance in animals. The present study accessed the possible role of supraspinal NO on antinociceptive effect of morphine in morphine tolerance using a highly specific inhibitor of the neuronal isoform of NOS, 1-(2-trifluoromethylphenyl) imidazole (TRIM). Methods: Thirty two male SD rats (300 g) were prepared with intracerebroventricular (icv) and IV cannulae. We administrated IV morphine, 3 mg/kg, daily for 4 days, resulting in tolerance. On the fifth day, a challenge dose of morphine, 3 mg/kg, was administered following pretreatment with icv TRIM, $10{\mu}g$. We also evaluated the antinociceptive effect of icv TRIM alone and the effect on a single dose of morphine (3 mg/kg) in morphine nave rats. Antinociception from morphine was determined by response to intraplantar injection of 5% formalin $100{\mu}l$ was qualified as the number of flinches in the first 0-10 min (first phase), 10-40 min Phase IIa, and 40-60 min (Phase IIb). Results: Pretreatment with icv TRIM significantly enhanced the antinociceptive effects of systemically administered morphine in morphine tolerant rats. The antinociceptive effect of morphine in opioid nave rats was also significantly increased by pretreatment with icv TRIM. Conclusions: Our results further support the hypothesis that supraspinal NO modulates morphine-sensitive nociceptive process in morphine tolerance due to chronic intravenous administration.

• Journal of the Korean Chemical Society
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• v.54 no.4
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• pp.363-373
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• 2010

Computational studies were carried out on the opiates morphine, heroin, codeine, pentazocine, and buprenorphine, under the density functional theory. The geometric parameters of the pharmacophore and substituents were evaluated at the B3LYP/6-31+G(d) level of theory. The electronic structure calculations were performed using the same hybrid functional at the B3LYP/6-311++G (d,p) level of theory. The atomic charges were obtained by Mulliken population analysis. Given the reported biological activity, calculated partition coefficients, and electronic and geometric analysis, pentazocine and buprenorphine were chosen as models for proposed analogues. These analogues were then studied and compared with the model molecules. The study reveals that the geometry and electronic structure of the pharmacophore remains consistent in the presence of different substituents. Because the proposed analogues preserve the studied properties of the model molecules, it is likely that these analogues display biological activity.

• YAKHAK HOEJI
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• v.29 no.1
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• pp.27-31
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• 1985

The administraction of ginseng butanol fraction(GBF) inhibited the development of tolerance to and physical dependence on morphine induced by morphine multiple injections in mice. Each group of mice was injected with morphine hydrochloride (40mg/kg s.c.) three times at 8 hr intervals for a period of 6 days. GBF (25, 50, 100, 200mg/kg) was injected (i.p.) to mice 1hr prior to the third morphine injection daily. Inhibition of morphine tolerance by GBF was evidenced by the increase in analgesic response to morphine hydrochloride (10mg/kg) as estimated by the tail flick method and the reduction in morphine dependence was estimated by the decreased number of the naloxone induced withdrawal jumping mice. Further evidenced that GBF reduced the development of morphine dependence was indicated by the fact that GBF decreased the loss in body weight.

• Journal of Hospice and Palliative Care
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• v.21 no.1
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• pp.9-13
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• 2018

Purpose: The purpose of this study was to assess the factors influencing the rescue medication decisions for breakthrough cancer patients and evaluate treatments using the factors. Methods: Based on the results of an online survey conducted by the Korean Society of Hospice and Palliative Care from September 2014 through December 2014, we assessed the level of agreement on nine factors influencing rescue medication preference. The same factors were used to evaluate oral transmucosal fentanyl lozenge, oral oxycodone and intravenous morphine. Results: Agreed by 77 physicians, a rapid onset of action was the most important factor for their decision of rescue medication. Other important factors were easy administration, strong efficacy, predictable efficacy and less adverse effects. Participants agreed that intravenous morphine produced a rapid onset of action and strong and predictable efficacy and cited difficulty of administration and adverse effects as negative factors. Oral oxycodone was desirable in terms of easy administration and less adverse effects. However, its onset of action was slower than intravenous morphine. While many agreed to easy administration of oral transmucosal fentanyl lozenge, the level of agreement was low for strength and predictability of its efficacy, long-term durability and sleep improvement. Conclusion: Rapid onset of action is one of the important factors that influence physicians' selection of rescue medication. Physicians' assessment of rescue medication differed by medication.

• Journal of Hospice and Palliative Care
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• v.20 no.1
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• pp.18-25
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• 2017

Purpose: Adequate control of breakthrough pain is essential for patients with cancer. Managing breakthrough pain mainly depends on understanding the concept of breakthrough pain and the proper usage of rescue medication by physicians. This study aims to assess the attitudes and practice patterns of palliative physicians in managing breakthrough pain for patients in Korea. Methods: This study was based on data from the 2014 breakthrough cancer pain survey conducted by the Korean Society for Hospice and Palliative Care. One hundred physicians participated in the online survey. Among total 33 self-reported questionnaires, twelve items were selected in this analysis. Results: Rapid onset of action is the main influencing factor in selecting rescue opioids. Oral oxycodone (65%) and parenteral morphine (27%) are commonly used. A few physicians (3%) prefer to use transmucosal fentanyl. The percentage of physicians prescribing oral oxycodone due to its rapid onset of action is just 21.5%, whereas the percentage of physicians using parenteral morphine is 81.5%. Two thirds of respondents (66%) answered that breakthrough pain is not well controlled with rescue medications. Conclusion: There is a gap between the needs of physicians in terms of the perceived difficulties of managing breakthrough cancer pain and their practice patterns selecting rescue medications.