• The Korean Journal of Pain
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• 제37권1호
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• pp.41-50
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• 2024

Background: Recognizing the seriousness of the misuse and abuse of medical narcotics, the South Korean government introduced the world's first narcotic management system, the Narcotics Information Management System (NIMS). This study aimed to explore the recent one-year opioid prescribing patterns in South Korea using the NIMS database. Methods: This study analyzed opioid prescription records in South Korea for the year 2022, utilizing the dispensing/administration dataset provided by NIMS. Public data from the Korean Statistical Information Service were also utilized to explore prescription trends over the past four years. The examination covered 16 different opioid analgesics, assessed by the total number of units prescribed based on routes of administration, type of institutions, and patients' sex and age group. Additionally, the disposal rate for each ingredient was computed. Results: In total, 206,941 records of 87,792,968 opioid analgesic units were analyzed. Recently, the overall quantity of prescribed opioid analgesic units has remained relatively stable. The most prescribed ingredient was oral oxycodone, followed by tapentadol and sublingual fentanyl. Tertiary hospitals had the highest number of dispensed units (49.4%), followed by community pharmacies (40.2%). The highest number of prescribed units was attributed to male patients in their 60s. The disposal rates of the oral and transdermal formulations were less than 0.1%. Conclusions: Opioid prescription in South Korea features a high proportion of oral formulations, tertiary hospital administration, pharmacy dispensing, and elderly patients. Sustained education and surveillance of patients and healthcare providers is required.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 춘계학술대회
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• pp.21-37
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• 2003

1. Stimulation of dopaminergic system by morphine was abolished in ${\mu}$-opioid receptor knockout mice. 2. Dopaminergic stimulation by opioid agonists, morphine, DPDPE, and U50488, acts independently. 3. Loss of ${\mu}$-opioid receptors is more sensitive to the response of NMDA-induced convulsion and increase in the expression of mRNA for NMDA receptors.

• The Korean Journal of Pain
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• 제35권4호
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• pp.413-422
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• 2022

Background: The neocortex, including the medial prefrontal cortex (mPFC), contains many neurons expressing nitric oxide synthase (NOS). In addition, increasing evidence shows that the nitric oxide (NO) and opioid systems interact in the brain. However, there have been no studies on the interaction of the opioid and NO systems in the mPFC. The objective of this study was to investigate the effects of administrating L-arginine (L-Arg, a precursor of NO) and N(gamma)-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NOS) into the mPFC for neuropathic pain in rats. Also, we used selective opioid receptor antagonists to clarify the possible participation of the opioid mechanism. Methods: Complete transection of the peroneal and tibial branches of the sciatic nerve was applied to induce neuropathic pain, and seven days later, the mPFC was cannulated bilaterally. The paw withdrawal threshold fifty percent (50% PWT) was recorded on the 14th day. Results: Microinjection of L-Arg (2.87, 11.5 and 45.92 nmol per 0.25 µL) increased 50% PWT. L-NAME (17.15 nmol per 0.25 µL) and naloxonazine (an antagonist of mu opioid receptors, 1.54 nmol per 0.25 µL) inhibited anti-allodynia induced by L-Arg (45.92 nmol per 0.25 µL). Naltrindole (a delta opioid receptor antagonist, 2.45 nmol per 0.25 µL) and nor-binaltorphimine (a kappa opioid receptor antagonist, 1.36 nmol per 0.25 µL) were unable to prevent L-Arg (45.92 nmol per 0.25 µL)-induced antiallodynia. Conclusions: Our results indicate that the NO system in the mPFC regulates neuropathic pain. Mu opioid receptors of this area might participate in pain relief caused by L-Arg.

• 보건행정학회지
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• 제31권4호
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• pp.409-422
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• 2021

The growing use of prescription analgesic opioids has rapidly escalated the treatment of chronic pain since the 1990s; however, it is also highly needed to control opioid-related issues, including opioids misuse, abuse, and addiction. In 2018, Organization for Economic Cooperation and Development (OECD) secretariat administered the survey on opioids use and policies to OECD countries and presented it at the Health Committee meeting of December 2018. This study aimed to review the opioids use in OECD countries and their policies to prevent and reduce associated harms, also seek the available policy lessons from OECD countries. More recently, opioids prescribing rate have been increased 14.7% between 2011-2013 and 2014-2016 and steadily focused on the main substance misused and abused in Korea. In addition, policy efforts have contributed to developing a guideline for prescribing opioids to steer the appropriate use of prescription analgesic opioids since 2000 in Korea, so it is not enough to control opioids compared with other OECD countries. Therefore, taking a people-centered and public health perspective, it will consider the health system policies and interventions at a national level to improve their preparation and approach to control opioid-related issues.

• The Korean Journal of Physiology and Pharmacology
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• 제4권4호
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• pp.291-299
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• 2000

Morphine or butorphanol was continuously infused into cerebroventricle (i.c.v.) with the rate of $26\;nmol/{\mu}l/h$ for 3 days, and the withdrawal from opioid was rendered 7 hrs after the stopping of infusion. The expression of physical dependence produced by these opioids was evaluated by measuring the naloxone-precipitated withdrawal signs. The withdrawal signs produced in animals dependent on butorphanol (kappa opioid receptor agonist) were similar to those of morphine (mu opioid receptor agonist). Besides the behavioral modifications, opioid withdrawal affected G protein expression in the central nervous system. The G-protein ${\alpha}-subunit$ has been implicated in opioid tolerance and withdrawal. The effects of continuous infusion of morphine or butorphanol on the modulation of G protein ${\alpha}-subunit$ mRNA were investigated by using in situ hybridization study. In situ hybridization showed that the levels of $G\;{\alpha}s$ and $G\;{\alpha}i$ were changed during opioid withdrawal. Specifically, the level of $G\;{\alpha}s$ mRNA was decreased in the cortex and cerebellar granule layer during the morphine and butorphanol withdrawal. The level of $G\;{\alpha}i$ mRNA was decreased in the dentate gyrus and cerebellar granule layer during the morphine withdrawal. However, the level of $G\;{\alpha}i$ mRNA was significantly elevated during the butorphanol withdrawal. These results suggest that region-specific changes of G protein ${\alpha}-subunit$ mRNA were involved in the withdrawal from morphine and butorphanol.

• 대한약리학회지
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• 제24권2호
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• pp.153-164
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• 1988

The potential role of endogenous opioid peptides (EOPS) in cardiovascular regulation has only recently been entertained. EOPS have been localized in brain, spinal cord, autonomic ganglia, particularly the adrenal gland, and many other peripheral tissues. There are at least five major types of opioid receptors; namely ${\mu},\;{\delta},\;k,\;{\sigma},\;and\;{\varepsilon}$ and Experimental evidence indicates that cardiovascular actions of the peptide are mediated primarily by ${\mu},\;{\delta}$ and k receptors, and that these receptor types may be allosterically coupled. In anesthetized rabbits met-enkephalin decreased blood pressure and heart rate, which closely paralleled a reduction in sympathetic discharge. Naloxone, but not naloxone methobromide, antagonized these effects, which suggests a central site of action of met-enkephalin. A number of autonomic agents, particularly adrenergic ${\alpha}$-and, ${\beta}-agonists$ and antagonists modify the cardiovascular actions of met-enkephalin. Experiments in reserpine-treated and adrenalectomized rats provide no evidence of sympathetic nervous system involvement in the pressor responses to intravenous injection of opioid peptides, but rather suggest a direct peripheral action. Finally, activation of a beta-endorphinergic pathway projecting from the arcuate nucleus to the nucleus tractos solitarii in rats can cause naloxone reversible hypotension and bradycardia. There is evidence to implicate this pathway in antihypertensive drug action and in the modulation of baroreflex activity.

• Journal of Dairy Science and Biotechnology
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• 제24권2호
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• pp.21-24
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• 2006

The ubiquitous presence of lactoferrin(LF) receptor in human as reported by the research group of Prof. Bo Lonnerdal, Univ. California (Suzuki, Y. A.,2001) encouraged us to search for the unknown physiological roles of Lf. Under the collaboration with Prof. Etsumori Harada, Tottori Univ., and his research group, we have found two novel biological activities of LF as the control of the lipid metabolism and the effect on the central nervous system. Relating to the lipid metabolism, LF could, in animal experiments, reduce triglyceride and total cholesterol both in blood and liver (Takeuchi, T et αl., 2003). LF increased plasms HDL-C and lowered LDL-C. In the central nervous system, LF showed anti-nociceptive activity mediated by ${\mu}$-opioid receptor in the rat spinal cord (Hayashida, K. et al., 2003). LF enhanced analgesic action of morphine synergistically via nitric oxide synthesis (Hayashida, K., et al., 2003) LF showed opioid-mediated suppressive effect on distress induced by maternal separation in rat pups (Takeuchi, T., et al., 2003).

• Toxicological Research
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• 제11권1호
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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.

• Journal of Acupuncture Research
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• 제22권3호
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• pp.23-35
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• 2005

본 연구에서는 전침자극이 면역계의 THl/TH2 분화평형에 미치는 영향과 opioid system 과의 관계를 알아보고자 DNP-KLH의 자극을 통해 IgE 매개 알러지 반응모델을 구축하고 족삼리(足三里).에 전침자극을 가한 후 TH1/TH2 분화평형 및 opioid receptor antagonist인 naloxone에 의 한 반전여부를 확인하기 위해 total IgE, antigen-specific IgE, IFN-${\gamma}$ 및 IL-4 mRNA 발현량을 측정하여 다음과 같은 결과를 얻었다. 1. 전침자극은 DNP-KLH로 인해 과도하게 생산 된 혈청 total IgE 및 antigen-specific IgE를 감소시킴으로서 알러지 반응에 대한 유의한 억제능을 발휘하였으며, naloxone 투여로 전침 의 효과가 상쇠된 것으로 미루어 opioid system이 전침에 의한 항알러지 효과에 중요한 역할을 하는 것으로 추정된다. 2. 또한 전침자극은 DNP-KLH로 인한 TH2 cytokine의 편향상태에 대하여 TH1/TH2 평형조절능을 가진다는 것을 확인하였으며, naloxone으로 반전되지 않는 것으로 미루어 전침이 미치는 보조 T cell 분화에 대한 효과 는 opioid system에 의존하지 않는 것으로 추정된다.

• Journal of Acupuncture Research
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• 제20권2호
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• pp.85-97
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• 2003

Introduction : In this study, the analgesic effect and its mechanism of bee venom aqua-acupuncture on complete Freund's adjuvant-induced arthritis in rats was investigated. It has been reported from a neurochemical standpoint that bee venom exerts antinociceptive effects on inflammation and that the opioid system and adrenergic system play important roles in acupuncture analgesia. however, it is not known whether central opioid and ${\alpha}2$-adrenergic components of the intrinsic descending analgesic system are activated after bee venom aqua-acupuncture. Methods : Bee venom(1mg/kg) was subcutaneously aqua-acupunctured into Joksamni($ST_{36}$) of rats with complete Freund's adjuvant(CFA)- induced arthritis and was checked of increase in TFL. Opioid and ${\alpha}_2$-adrenergic neurotransmitter system were examined by naloxone as an opioid receptor antagonist, and yohimbine as ${\alpha}_2$-adrenoceptor antagonist prior to bee venom aqua-acupuncture. Results : The following results have been obtained. 1. The tail flick latency in the rat model with adjuvant-induced arthritis was significantly decreased in 2 weeks. 2. The tail flick latency in the rat model with adjuvant-induced arthritis was increased in bee venom aqua-acupuncture group compared to the normal saline aqua-acupuncture group. 3. Analgesic effect of bee venom was antagonized by yohimbine not by naloxone pretreatment in the rat model adjuvant-induced arthritis. Conclusions : Bee venom aqua-acupuncture has an analgesic effect on the rat model of adjuvant-induced of adjuvant-induced arthritis and has antinociception mediated by ${\alpha}_2$-adrenergic system.