• The Korean Journal of Pain
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• 제32권2호
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• pp.87-96
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• 2019

Background: This study was performed in order to examine the effect of intrathecal sec-O-glucosylhamaudol (SOG), an extract from the root of the Peucedanum japonicum Thunb., on incisional pain in a rat model. Methods: The intrathecal catheter was inserted in male Sprague-Dawley rats (n = 55). The postoperative pain model was made and paw withdrawal thresholds (PWTs) were evaluated. Rats were randomly treated with a vehicle (70% dimethyl sulfoxide) and SOG ($10{\mu}g$, $30{\mu}g$, $100{\mu}g$, and $300{\mu}g$) intrathecally, and PWT was observed for four hours. Dose-responsiveness and ED50 values were calculated. Naloxone was administered 10 min prior to treatment of SOG $300{\mu}g$ in order to assess the involvement of SOG with an opioid receptor. The protein levels of the ${\delta}$-opioid receptor, ${\kappa}$-opioid receptor, and ${\mu}$-opioid receptor (MOR) were analyzed by Western blotting of the spinal cord. Results: Intrathecal SOG significantly increased PWT in a dose-dependent manner. Maximum effects were achieved at a dose of $300{\mu}g$ at 60 min after SOG administration, and the maximal possible effect was 85.35% at that time. The medial effective dose of intrathecal SOG was $191.3{\mu}g$ (95% confidence interval, 102.3-357.8). The antinociceptive effects of SOG ($300{\mu}g$) were significantly reverted until 60 min by naloxone. The protein levels of MOR were decreased by administration of SOG. Conclusions: Intrathecal SOG showed a significant antinociceptive effect on the postoperative pain model and reverted by naloxone. The expression of MOR were changed by SOG. The effects of SOG seem to involve the MOR.

• 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.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• 제23권6호
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• pp.427-448
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• 2019

Nociceptin/orphanin FQ (N/OFQ) and its receptor, nociceptin opioid peptide (NOP) receptor, are localized in brain areas implicated in depression including the amygdala, bed nucleus of the stria terminalis, habenula, and monoaminergic nuclei in the brain stem. N/OFQ inhibits neuronal excitability of monoaminergic neurons and monoamine release from their terminals by activation of G protein-coupled inwardly rectifying $K^+$ channels and inhibition of voltage sensitive calcium channels, respectively. Therefore, NOP receptor antagonists have been proposed as a potential antidepressant. Indeed, mounting evidence shows that NOP receptor antagonists have antidepressant-like effects in various preclinical animal models of depression, and recent clinical studies again confirmed the idea that blockade of NOP receptor signaling could provide a novel strategy for the treatment of depression. In this review, we describe the pharmacological effects of N/OFQ in relation to depression and explore the possible mechanism of NOP receptor antagonists as potential antidepressants.

• The Korean Journal of Pain
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• 제20권2호
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• pp.100-105
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• 2007

Background: Ginseng has been used to manage various types of pain in folk medicine. This study characterized the effect of treatment with intrathecal ginsenosides, the active components of ginseng in a postoperative pain model. Methods: Male Sprague-Dawley rats were implanted with lumbar intrathecal catheters. An incision was made in the plantar surface of the hindpaw. Withdrawal thresholds following the application of a von Frey filament to the wound site were measured. To determine the role of the opioid or GABA receptors following treatment with the ginsenosides, naloxone, bicuculline (a $GABA_A$ receptor antagonist), and saclofen (a $GABA_B$ receptor antagonist) were administered intrathecally 10 min before the delivery of the ginsenosides and the changes of the withdrawal thresholds after application of the von Frey filament were Observed. Results: Treatment with the intrathecal ginsenosides increased the withdrawal threshold in a dose dependent manner. Pre-treatment with intrathecal naloxone reversed the antinociceptive effect of the ginsenosides. However, pre-treatment with intrathecal bicuculline and saclofen failed to have an effect on the activity of the ginsenosides. Conclusions: These results suggest that ginsenosides are effective to alleviate the postoperative pain evoked by paw incision. The opioid receptor, but not GABA receptors, may be involved in the antinociceptive action of the ginsenosides at the spinal level.

• 대한정형외과학회지
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• 제55권1호
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• pp.1-8
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• 2020

고령화의 진행 및 근골격계 질환의 증가로 인해 여러 가지 수술적 치료 방법을 포함한 침습적인 치료 방법이 증가되고 있으나 수술적 치료 시행 전 보존적 치료는 충분히 시행되어야 한다. 보존적 치료 중에서 통증 조절을 위한 약물 치료는 오래 전부터 보존적 치료의 가장 대표적인 치료 방법으로 사용되어 왔고 여전히 가장 흔히 사용되는 방법이다. 통증 조절을 위한 약물로는 아세트아미노펜(acetaminophen), 비스테로이드성 항염증제(non-steroidal anti-inflammatory drugs), 스테로이드(steroid), 마약성 진통제(opioid), 항우울제(antidepressants) 등이 있으며 저자는 마약성 진통제 및 항우울제에 대해서 살펴보고자 한다. 통증으로 인해 말초 부위에 있는 통각 수용체에 자극이 전달되면 통증은 중추 신경계로 전달되는 상향성 경로(ascending pathway)를 거쳐 대뇌에 전달되고 대뇌는 통증을 조절하기 위해 하향성 조절 경로(descending pathway)를 통해 엔도르핀(endorphin)과 같은 내인성 마약성 진통제를 분비하게 된다. 마약성 진통제라는 것은 마약성 진통제 수용체(receptor)에 작용하는 물질을 통틀어서 일컫는 말로 마약성 진통제는 세 가지의 수용체가 존재하며 조직이나 환자의 전신 상태에 따라서 각각의 수용체에 대한 친화성이 달라진다. 이와는 달리 항우울제는 중추신경계의 시냅스에 작용하여 통증을 조절하는 상향성 경로를 조절하는 것이 주된 기전으로 만성통증과 신경병성 통증에 효과적이며 이는 마약성 진통제 계열과 효과가 유사한 것으로 알려져 있다. 본 종설에서는 이러한 마약성 진통제와 항우울제의 효과적인 사용 방법, 사용 시 유의점 및 부작용 등에 대해 다루고자 한다.

• Journal of Ginseng Research
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• 제19권3호
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• pp.219-224
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• 1995

The modulatory effects of total ginseng saponin (TGS) on the 1, 6, and opioid receptor binding in morphine tolerance and dependence were examined in this study. The specific [$^{3}H$]DAGO ([D-$Ala^2$, N-$Mephe^4$, $Glyco^4$] enkephalin) binding was significantly increased in chronic morphine (10 mg/kg, i.p.) treated mouse striatum. The specific [$^{3}H$]DPDPE ([D-$Pen^2$, D-$Pen^5$] enkephalin) binding was ignificantly increased following morphine treatment in the mouse striatum and cortex. Also, an apparent decrease in the affinity of [$^{3}H$]DPN (diprenorphine) was observed after chronic morphine treatment in mouse striatum and cortex. 7GS produced a sleight increase of specific [$^{3}H$]DAGO, [$^{3}H$]DPDPE binding and a significant increase of specific [$^{3}H$]DPN binding in the mouse brain striatum. In cortex, TGS produced an inhibition of specific [$^{3}H$]DAGO and [$^{3}H$]DPDPE binding and increase of the specific [$^{3}H$]DPN binding. The prolonged administration of TGS (25, 50, 100, and 150 mg/kg, i.p., 3 wks) produced an inhibition of increased [$^{3}H$]DAGO specific binding following morphine without significant changes in the agonist binding to and receptors in mouse striatum and cortex. These contracted alterations in $\mu$, $\gamma$ and $\kappa$ opiate receptor binding were dependent in TGS dogs and brain sites.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.152-153
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• 1998

Oxytocin (OT) is a neurohypophyseal nonapeptide which plays an important role in CNS function as well as uterine contraction during delivery. Furthermore, recently it has been reported that OT may also have analgesic effect and found that the release of OT is related with opioid receptors, especially $\kappa$ and ${\mu}$.

• The Korean Journal of Physiology and Pharmacology
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• 제5권6호
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• pp.479-485
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• 2001

The existence of opioid receptors in mammalian cerebellum except human, has not been clearly understood. In the present study, we found that NPY was inducible by morphine in the mouse cerebellar granular and Purkinje cell layers. We performed in situ RT-PCR and immunohistochemistry to characterize the NPY expression. The increase of NPY gene expression by morphine (30 mg/kg, i.p.) was inhibited by pretreatment with not only naloxone (100 mg/kg, i.p.) but also a noncompetitive NMDA antagonist, MK-801 (0.3 mg/kg, i.p.). The competitive NMDA antagonist, AP-5 (0.9 mg/kg, i.p.) slightly attenuated the increased NPY expression by morphine. Also, the finding similar to morphine was shown by NMDA (70 mg/kg, i.p.) treatment. Our results indicate that NPY was inducible by morphine and this might reflect activation of NMDA receptors in granule cells that relay mossy fiber inputs to Purkinje cells via parallel fibers.

• Natural Product Sciences
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• 제12권1호
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• pp.14-18
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• 2006

The effect(s) of the volatile oil (VO) of Nigella sativa and its two components, ${\alpha}-pinene$ and ${\rho}-cymene$ on body temperature of male and female conscious mice were studied. Further investigations to delineate the mechanism(s) of action of the observed effect(s) by using various blockers involved in the central regulation of body temperature were made. VO and ${\alpha}-pinene$ caused significant reductions in rectal body temperature at is and 30 minute after treatment. ${\rho}-cymene$ had negligible effect on body temperature of mice. Cyproheptadine inhibited VO and ${\alpha}-pinene-induced$ hypothermia significantly. Nalbuphine inhibited ${\alpha}-pinene-induced$ hypothermia significantly but did not affect VO-induced hypothermia. Droperidol potentiated VO and ${\alpha}-pinene-induced$ hypothermia to a non-significant level; whereas atropine potentiated VO-induced hypothermia non-significantly. The study confirms further the role of serotoninergic receptors in the mechanism(s) of the observed pharmacological effects of the VO of Nigella sativa. It also indicated a possible role of opioid receptors in ${\alpha}-pinene-induced$ hypothermia.