• Archives of Pharmacal Research
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• 제16권2호
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• pp.83-88
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• 1993

opioid pure agonists, morphine, meperidine and methadone, were used to investigate the effect on the opioid receptor of fron sciatic nerve fibers using sucrose gap apparatus. When applied extracellularly by perfusion, morphine, methadone and meperidine significantly depressed the amplitude of the action potential in frog sciatic nerve fibers as a dose-dependent $(10^{-10}\;M-10^{-2}\;M)$ manner. The depression with morphine or methadone was partially antagonized by the simultaueous treatment with a lower $(10^{-10}\;M-10^{-8}\;M)$ concentration of naloxone, but that of meperidine was not blocked. When the three opioid agonists were applied intracellularly by placing it in a compartment with a cut end of the sciatic nerve fibers, all of themn depressed the amplitude of the action potentials by similar potency, and these reductions significantly blocked by pretreatment of lower concentration $(10^{-10}\;M-10^{-8}M)$ of naloxone. These results support the previous findings by other workers that the stereospecific opioid receptors of this preparation are located on or near the intracellular opening of the sodium channels which are sensitive to naloxone.

• The Korean Journal of Pain
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• 제35권4호
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• pp.433-439
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• 2022

Background: Repeated administration of opioid analgesics for pain treatment can produce paradoxical hyperalgesia via peripheral and/or central mechanisms. Thus, this study investigated whether spinally (centrally) administered orexin A attenuates opioid-induced hyperalgesia (OIH). Methods: [D-Ala², N-Me-Phe⁴, Gly⁵-ol]-enkephalin (DAMGO), a selective µ-opioid receptor agonist, was used to induce mechanical hypersensitivity and was administered intradermally (4 times, 1-hour intervals) on the rat hind paw dorsum. To determine whether post- or pretreatments with spinal orexin A, dynorphin A, and anti-dynorphin A were effective in OIH, the drugs were injected through an intrathecal catheter whose tip was positioned dorsally at the L3 segment of the spinal cord (5 ㎍ for all). Mechanical hypersensitivity was assessed using von Frey monofilaments. Results: Repeated intradermal injections of DAMGO resulted in mechanical hypersensitivity in rats, lasting more than 8 days. Although the first intrathecal treatment of orexin A on the 6th day after DAMGO exposure did not show any significant effect on the mechanical threshold, the second (on the 8th day) significantly attenuated the DAMGO-induced mechanical hypersensitivity, which disappeared when the type 1 orexin receptor (OX1R) was blocked. However, intrathecal administration of dynorphin or an anti-dynorphin antibody (dynorphin antagonists) had no effect on DAMGO-induced hypersensitivity. Lastly, pretreatment with orexin A, dynorphin, or anti-dynorphin did not prevent DAMGO-induced mechanical hypersensitivity. Conclusions: Spinal orexin A attenuates mechanical hyperalgesia induced by repetitive intradermal injections of DAMGO through OX1R. These data suggest that OIH can be potentially treated by activating the orexin A-OX1R pathway in the spinal dorsal horn.

• The Korean Journal of Physiology and Pharmacology
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• 제16권3호
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• pp.187-192
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• 2012

In the present study, the antinociceptive profiles of hop extract were characterized in ICR mice. Hop extract administered orally (from 25 to 100 mg/kg) showed an antinociceptive effect in a dose-dependent manner as measured in the acetic acid-induced writhing test. Antinociceptive action of hop extract was maintained at least for 60 min. Moreover, cumulative response time of nociceptive behaviors induced with intraplantar formalin injection was reduced by hop extract treatment during the 2nd phases. Furthermore, the cumulative nociceptive response time for intrathecal injection of substance P ($0.7{\mu}g$) or glutamate ($20{\mu}g$) was diminished by hop extract. Intraperitoneal pretreatment with naloxone (an opioid receptor antagonist) attenuated antinociceptive effect induced by hop extract in the writhing test. However, methysergide (a 5-HT serotonergic receptor antagonist) or yohimbine (an ${\alpha}_2$-adrenergic receptor antagonist) did not affect antinociception induced by hop extract in the writhing test. Our results suggest that hop extract shows an antinociceptive property in various pain models. Furthermore, the antinociceptive effect of hop extract may be mediated by opioidergic receptors, but not serotonergic and ${\alpha}_2$-adrenergic receptors.

• Bulletin of the Korean Chemical Society
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• 제30권3호
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• pp.599-607
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• 2009

A series of conjugated cyclic and linear enkephalin analogs, Tyr-c[D-A2bu-Gly-Phe-Asp(NH-X)], where X = methyl, stearyl or$ PEG_350$, and Tyr-D-Ala-Gly-Phe-Cys(S-X), where X = methyl, octyl, or farnesyl, were synthesized in solution to investigate the receptor selectivity of opioids based on Schwyzer's membrane compartment $concepts.^{5,6}$ Cyclizations of the target compounds were achieved in high yields (> 60%) employing BOP, $NaHCO_3$ in DMF despite the steric hindrance of the bulky pendant groups. In the binding assay, the hydrophobic fatty acyl conjugates retained $\mu$-receptor selectivity. The unsaturated farnesyl conjugate exhibited the increased binding affinity than the saturated stearyl conjugate for both $\mu$-and $\delta$-opioid receptors. The PEG conjugates displayed the $\delta$-receptor selectivity. The low molecular weight $PEG_350$ conjugate exhibited the increase selectivity than the high molecular weight $PEG_5000$ conjugate to the $\delta$-receptor. The results of this study support the membrane compartment concepts.

• Advances in Traditional Medicine
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• 제7권4호
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• pp.390-394
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• 2007

The present study was conducted to evaluate the analgesic activity of ethanolic extract of Andrographis paniculata (AP) in mice. The analgesic investigations were carried out using the acetic acid-induced abdominal writhing and the hot-plate tests. It was demonstrated that intraperitoneal (i.p.) administration of the extract at a dose of 30, 100, 300, 500 mg/kg, produced significant inhibition of abdominal constriction induced with 0.6% (v/v) acetic acid in dosedependent manner. It also demonstrated that the extract produced significant dose-dependent increase in the time of latency to a discomfort reaction in the hot-plate model. In addition, the analgesic effect of the ethanolic extract of AP was significantly reversed by a non-specific opioid receptor antagonist, naloxone. These results indicate that AP has an analgesic effect that was mediated through opioid receptors.

• Journal of Hospice and Palliative Care
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• 제21권4호
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• pp.152-157
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• 2018

암환자에서 암성 통증을 완화시키기 위한 강한 마약성 진통제의 사용이 늘어남에 따라, 마약성 진통제 관련 이상행동이 새로운 문제로 대두되고 있다. 비암성 환자에서의 마약성 진통제에 대한 중독 및 신체적 의존의 치료는 잘 알려져 있으나, 암환자, 특히 국내의 암환자에서는 이와 관련한 연구가 부족한 실정이다. 본 저자들은 강한 마약성 진통제에 대해 신체적 의존을 보여 부분 뮤-아편양 수용체 작용제인 buprenorphine으로 성공적으로 치료 받았던 열 명의 암환자들을 보고하고자 한다. 이는 암환자의 마약성 진통제에 대한 신체적 의존을 경피적 buprenorphine 패취로 치료할 수 있음을 보여준 첫 번째 보고이다.

• 생약학회지
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• 제47권1호
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• pp.38-42
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• 2016

Caragana sinica (Leguminosae) is a plant, which has been used as a traditional medicine for the treatment of lots of diseases including neuralgia, goat, hypertension and eczema. However, scientific studies of C. sinica in pharmacological aspects are not carried out. In this study, the anti-nociceptice effect of methanolic extract of C. sinica (MCS) was evaluated using various pain models. Our data represented that MCS significantly delayed the latency time under central pain condition which are arose from thermal stimuli, indicating MCS possess analgesic potential against central nociception. In addition, MCS showed strong and dose-dependent anti-nociceptive activities on acetic acid-induced peripheral pain, compared to positive control such as indomethacin. Further combination studies using naloxone, a non-selective opioid receptor antagonist, have revealed that analgesic activity of MCS was not changed in the presence of naloxone, indicating MCS exerts anti-nociceptive activity independent of opioid receptor. These results suggest that MCS may be an effective medicine in managing pain.

• 한국유가공학회:학술대회논문집
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• 한국유가공기술과학회 2005년도 제61회 국제 유가공 심포지움
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• pp.1-9
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• 2005

The ubiquitous presence of lactoferrin (LF) receptor in human as reported by the research group of Prof, Bo Lonnerdal, Univ. California, 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. LF increased plasma 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. LF enhanced analgesic action of morphine synergistically via nitric oxide synthesis. LF showed opioid-mediated suppressive effect on distress induced by maternal separation in rat pups.

• 대한암한의학회지
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• 제25권2호
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• pp.37-49
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• 2020

Objective: Constipation is the most common adverse effect of opioid analgesic therapy in cancer patients. This can be associated with physical and emotional distress to cancer patients. The purpose of this study is to review the standard and alternative interventions of the management for opioid-induced constipation (OIC). Methods: The studies were searched from databases, including Pubmed, Google scholar, KISS, NDSL, and OASIS. The main search terms included such as constipation, opioid, opioid-induced constipation, cancer, management, herb, and acupuncture. Results: The prevention and usual care of constipation is a key tool for the management of OIC. Also, prophylactic laxatives starting concurrently with opiates helped to prevent developing constipation. Peripherally acting μ-opioid receptor antagonists (PAMORAs) significantly reduced OIC and well-tolerated. In addition, acupuncture, herb medicines, and interferential current or transcutaneous electrical nerve stimulation to acupoints had effectiveness in reducing constipation. Conclusion: Preliminary data indicate that PAMORAs and Traditional Korean Medicine may be considered as the management of unresolved OIC. However, due to the limited articles, more systematic and rigorous clinical trials are needed.

• The Korean Journal of Pain
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• 제30권2호
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• pp.98-103
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• 2017

Background: The root of Peucedanum japonicum Thunb., a perennial herb found in Japan, the Philippines, China, and Korea, is used as an analgesic. In a previous study, sec-O-glucosylhamaudol (SOG) showed an analgesic effect. This study was performed to examine the antinociceptive effect of intrathecal SOG in the formalin test. Methods: Male Sprague-Dawley rats were implanted with an intrathecal catheter. Rats were randomly treated with a vehicle and SOG ($10{\mu}g$, $30{\mu}g$, $60{\mu}g$, and $100{\mu}g$) before formalin injection. Five percent formalin was injected into the hind-paw, and a biphasic reaction followed, consisting of flinching and licking behaviors (phase 1, 0-10 min; phase 2, 10-60 min). Naloxone was injected 10 min before administration of SOG $100{\mu}g$ to evaluate the involvement of SOG with an opioid receptor. Dose-responsiveness and ED50 values were calculated. Results: Intrathecal SOG showed a significant reduction of the flinching responses at both phases in a dose-dependent manner. Significant effects were showed from the dose of $30{\mu}g$ and maximum effects were achieved at a dose of $100{\mu}g$ in both phases. The ED50 value (95% confidence intervals) of intrathecal SOG was 30.3 $(25.8-35.5){\mu}g$ during phase 1, and 48.0 (41.4-55.7) during phase 2. The antinociceptive effects of SOG ($100{\mu}g$) were significantly reverted at both phases of the formalin test by naloxone. Conclusions: These results demonstrate that intrathecal SOG has a very strong antinociceptive effect in the formalin test and it seems the effect is related to an opioid receptor.