• 대한수의학회지
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• 제39권1호
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• pp.45-54
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• 1999

In the present study we have analyzed the characteristics and distribution of the mu-opioid receptor(MOR) by raising anti-peptide antisera to the C-terminal peptide of MOR. The antisera against MOR was produced in New Zealand White rabbit against 15 residue corresponding to amino acids, 384-398 of the cloned rat MOR. The antigenic peptide was synthesized using an Applied Biosystems 432 solid-phase peptide synthesizer. The specificity and identification of the antisera were tested by analysis of transfected cells, epitope mapping and immunohistochemical method. COS-7 cells electroporated with MOR cDNA were used to evaluate the characteristics and subcellular distribution of MOR. MOR immunoreactivity was prodominent in the plasmalemma and subcellular compartments such as endoplasmic reticulum, Golgi apparatus and vesicle like structure. Furthermore, both tissue sections and transfected cell lines could be immunostained with these antisera and the immunoreactivity was abolished when anti-MOR sera were preincubated with the peptide against which they were raised. Based on epitope mapping analysis, all antisera appeared to have a similar epitope, which was determined to be within the last amino acid, 391-398. Moreover, immunohistochemistry showed that MOR immunoreactivity was observed in many brain areas including cerebral cortex, striatum, hippocampus, locus coeruleus and the superficial laminae of the dorsal horn. These stained spinal cord and brain areas showed the mirrored pattern observed in auto radiographic studies of mu-opioid binding as well as a pattern similar to that seen by is situ hybridization for MOR. Thus, several lines of evidence support the conclusion that the antisera produced in the present study most likely recognize mu-opioid receptor. These results suggest that MOR antisera may be utilized as useful tool to analyze the physiological and pharmacological studies for mu-opioid receptor in the future.

• The Korean Journal of Pain
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• 제20권1호
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• pp.21-25
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• 2007

Background: Intrathecal sildenafil has produced antinociception by increasing the cGMP through inhibition of phosphodiesterase 5. Spinal opioid receptor has been reported to be involved in the modulation of nociceptive transmission. The aim of this study was to examine the role of opioid receptor in the effect of sildenafil on the nociception evoked by formalin injection. Methods: Rats were implanted with lumbar intrathecal catheters. Formalin testing was used as a nociceptive model. Formalin-induced nociceptive behavior (flinching response) was observed. To clarify the role of the opioid receptor for the analgesic action of sildenafil, naloxone was administered intrathecally 10 min before sildenafil delivery, and formalin was then injected 10 min later. Results: Intrathecal sildenafil produced dose-dependent suppression of flinches in both phases during the formalin test. Intrathecal naloxone reversed the analgesic effect of sildenafil in both phases. Conclusions: Sildenafil is active against the nociceptive state that's evoked by a formalin stimulus, and the opioid receptor is involved in the analgesic action of sildenafil at thespinal level.

• The Korean Journal of Pain
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• 제24권1호
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• pp.7-12
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• 2011

Background: Adenosine has been shown to have a wide spectrum of unique pain-relieving effects in various clinical situations. The aim of this study was to investigate the effects of intraoperative adenosine infusion on acute opioid tolerance and opioid induced hyperalgesia induced by remifentanil in adult patients undergoing tonsillectomy. Methods: For this study, ninety patients were randomly allocated into groups that receive either adenosine (adenosine group) or saline (remifentnail group) intravenously under remifentanil based anesthesia and saline (sevoflurane group) under sevoflurane anesthesia. The patients in adenosine group received adenosine at dose of $80\;{\mu}g$/kg/min, and those in remifentnail group and sevoflurane group received an equal volume of saline 10 minutes after the induction of anesthesia until the end of surgery. Intraoperative evaluation included time weighted mean remifentanil dose, and postoperative evaluations included degree of pain severity at 1, 6, 12, and 24 hours, time to first postoperative requirement, and analgesic dose required during 24 hours after operation. Results: Time weighted mean remifentanil dose during intraoperative period in adenosine group was significantly lower than that of remifentnail group (P = 0.00). The first postoperative analgesic were required earlier in remifentanil group than sevoflurane group or adenosine group (P = 0.00). Pethidine requirement during 24 hours in sevoflurane group and adenosine group was significantly lower than that of remifentnail group (P = 0.00). The visual analog scale scores for pain in sevoflurane group and adenosine group were significantly lower than those of remifentnail group for 12 hours after operation (P = 0.00). Incidence of hypotension (P = 0.024) and number of ephedrine administered (P = 0.011) in adenosine group were significantly higher than those of sevoflurane group. Conclusions: The above results suggest that intraoperative adenosine infusion prevent acute opioid tolerance and opioid induced hyperalgesia induced by remifentanil.

• 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.

• 종양간호연구
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• 제1권2호
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• pp.157-167
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• 2001

Purpose : This study was 1) to determine the relationship between endogenous opioid-peptides and hope 2) to evaluate the availability of the opioid- peptides, known as biochemicals of emotion in psychoneuroimmunology, as a variable to explain hope. Method : blood sampling for 20 cancer patients' (age range 18-73, 13 men and 7 women, having mild pain or no pain, can do ADL) were made under approval from the doctors in a university hospital at 8 A.M. and quantitative analysis of opioid peptides were done by the internal standard method. In 10min after blood sampling, hope was measured using Kim and Lee's hope scale which had acceptable reliabilities and validity after making consent about interviewing. Blood was sampled from the seven normal adults for comparing the degrees of the opioids. None-parametric statistical analysis was used. Results : There was a significant difference in leucine enkephalin between normal adults and cancer patients. And significant positive relationship existed between chemotherapy and leucine enkephalin. So, the relationships between hope and the endogenous opioids in the patients before chemotherapy were re-tested, excluding the effect of chemotherapy on opioids. As a result, a significant negative relationship between hope and beta- endorphin(r=-.841<.05) showed. And there were highly negative relationships between leucine enkephalin and methionine enkephalin and hope, but not significant statistically. Conclusions : This results implies endogenous opioids can be used as a biological variable to explain hope. More researches in sophisticated design would be needed ,especially in human model.

• The Korean Journal of Pain
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• 제26권3호
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• pp.277-285
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• 2013

Background: Opioid analgesics are widely used to reduce postoperative pain and to enhance post-operative recovery. However, orthostatic intolerance (OI) induced by opioid containing intravenous patient controlled analgesia (IPCA) may hinder postoperative recovery. This study investigated factors that affect OI in patients receiving IPCA for postoperative pain control. Methods: OI was instantly evaluated at the time of first ambulation in 175 patients taking opioid containing IPCA after open and laparoscopic subtotal gastrectomies. Patients were classified as having OI if they experienced dizziness, nausea/vomiting, blurred vision, headache, somnolence and syncope. Factors contributing to OI were assessed with logistic regression analysis. Results: Out of 175 patients, 61 (52.6%) male and 44 (74.6%) female patients experienced OI at the time of first ambulation. The frequency of OI related symptoms were dizziness (97, 55.4%), nausea (46, 26.3%), headache (9, 5.1%), blurred vision (3, 1.7%) and vomiting (2, 1.1%). Significant risk factors for OI were gender (P=0.002) and total amount of opioids administered (P=0.033). Conclusions: The incidence of OI is significantly higher in male than in female patients and is influenced by the opioid dose.

• Biomolecules & Therapeutics
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• 제7권3호
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• pp.278-284
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• 1999

DK1001 is a thebain derivative, which is newly synthesized as an alkaloid analgesic. This study was designed to study effects of DK1001 on the ligands binding to the opioid receptor subtypes, and general pharmacology of DK1001. DK1001 inhibited the binding of [$^3H$]DAMGO, a selective mu-subtype agonist, to the opioid receptor of rat forebrain in a concentration-dependent manner. $EC_{50}$ of DK1001 was significantly lower than that of morphine. DK1001 inhibited the binding of 〔$^3$H〕DPDPE, a selective delta-subtype agonist concentration-dependently. DK1001(0.5 mg/kg) had no effects on behavior, body temperature, blood pressure. respiratory rate, and intestinal charcoal propulsion of mice. In addition, DK1001 did not affect on the contractilities of isolated muscle strips of aorta, ileum, and trachea of rats. These results suggest that DK1001 might be a potent analgesic without serious side effects.

• 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.

• Journal of Hospice and Palliative Care
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• 제27권1호
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• pp.45-49
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• 2024

Purpose: This study investigated palliative care physicians' attitudes regarding social issues related to opioid use. Methods: An email survey was sent to 674 physicians who were members of the Korean Society for Hospice and Palliative Care (KSHPC). Results: Data from 66 physicians were analyzed (response rate, 9.8%). About 70% of participants stated that their prescribing patterns were not influenced by social issues related to opioid use, and 90% of participants thought that additional regulations should be limited to non-cancer pain. Under the current circumstances, pain education for physicians is urgently needed, as well as increased awareness among the public. Half of the respondents identified the KSHPC as the primary organization responsible for providing pain education. Conclusion: Palliative care physicians' prescribing patterns were not influenced by social issues related to opioid use, and these issues also should not affect cancer pain control.

• 대한약리학회지
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• 제30권1호
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• pp.1-9
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• 1994

Opioid 수용체에는 ${\mu},\;{\delta}$ 그리고 ${\kappa}$의 세가지 주된 형이 존재함이 알려져 있는 바, 최근 수용체 동정 기법과 선택적인 약물의 개발로 인해 그 아류들이 존재함이 보고되고 있다. 그러나 Opioid ${\kappa}_{2-}$ 수용체의 기능에 대해서는 이 수용체에 있어서의 선택적인 효현제 또는 길항제가 밝혀져 있지 않으므로써 현재까지 잘 알려져 있지 않다. 본 연구에서는 백서 대뇌피질 세표막표본에 opioid ${\mu}$와 ${\delta}$ 수용체를 과량의 DAMGO와 DPDPE로 봉쇄한 후 수종 ${\kappa}$수용체 결합자의 $[^3H]\;idprenorpnine(DIP)$ 결합억제효과와 이에 대한 sodium과 $GTY{\gamma}S$의 영향을 관찰하여 이를 지표로 각 ligand의 수용체에서의 작용양상을 검토하여 이를 토대로 동일 표본에서 $[^3H]diprenorpnine[^3H]DIP$ 결합은 DIP, ethylketocyclazocine 그리고 bremazocine에 의해 효과적으로 억제되었으나, ${\kappa}_1$, 수용체 효현제인 U69593에 의해서는 억제되지 않았다. Opioid ${\kappa}_1$, 및 ${\kappa}_2$-수용체 효현제인 EKC의 Ki치는 배양액내 NaCl을 NMDG로 알려진 $GTP{\gamma}S\;100{mu}M$ 첨가에 의해 증가되었다. 그러나 Bremazocine과 DIP의 Ki치는 sodium 제거 또는 $GTP{\gamma}S\;100{mu}M$ 첨가에 의해 증가되었다. 그러나 Bremazocine과 DIP의 Ki치는 sodium 제거 또는 $GTP{\gamma}S$ 첨가에 의해 영향받지 않았다. $1-[^3H]\;histidine$을 미리 부하한 대뇌피질 절편에서 $30mM\;K^+$ 에 의한 $[^3H]\;histamine$의 유리는 (-)EKC에 의하여 영향받지 않았다. (-)EKC의 histamine유리 억제효과는 naloxone, norbinaltorpmine 또는 bremazocine에 의하여 각각 억제되었다. 본 실험 성적은 백서 대뇌피질에서 histamine의 유리는 이 부위에 존재하는 opioid ${\kappa}_2$-수용체에 의하여 조절됨을 시사한다.