• Journal of Ginseng Research
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• v.32 no.1
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• pp.1-7
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• 2008

Ginseng saponin has been shown to inhibit the development of dependence on morphine, cocaine, methamphetamine, but the antinarcotics effects of ginseng on nalbuphine remains still largely unknown. Ginseng administration attenuated the naloxone-induced jumping behavior on nalbuphine dependent mice. The development of morphine dependence was mediated through ${\mu}-opioid$ receptor, however, development of nalbuphine dependence was mediated through ${\kappa}-opioid$ receptor. However, it was found that the efficacy of analgesic antagonism of GTS was mediated through the serotonergic mechanism, not mediated through the opioid receptor. In addition, ginseng administration modulated cellular signal transduction in the brain. The increased NMDA receptor subunit (NR1, pNR1), phosphate extracellular signal regulated protein kinase (pERK), phosphate cAMP response element binding protein (pCREB) expression by nalbuphine was decreased by the administration of ginseng powder in cortex, hippocampus, striatum of rat brain. These results suggest that ginseng could be one of the targets of antinarcotic therapies to reduce the development of tolerance and dependence on nalbuphine as well as morphine.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.303-303
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• 1994

ICV infusion of morphine (MOR) produces strong analgesia in man and animals. The analgesic effect is thought to be mediated by the centrifugal inhibtory control, But neural mechanisms of the analgesic effect of ICV morphine are not well understood. For example, in the previous studies, ICV morphine does not inhibit nociceptive transmission in the spinal cord. On the contrary, ICV MOR often excites activity of dorsal horn neuron in the spinal cord. In the present study, we found that ICV MOR had dust actions on activity of dorsal horn neuron that it produced both inhibition and excitation of dorsal horn neurons. Since MOR exerts i Is action via three different types of opioid receptors, we further sought to investigate if there are differential effects of opioid receptor agonists on dorsal horn neurons when administered ICV.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.304.3-305
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• 2002

The present study investigated the passive avoidance and spatial learning in the ${\mu}$-opioid receptor gene knockout mice and wild type mice. In the step-through passive avoidance task. the ${\mu}$-opioid receptor knockout mice did not differ from the wild type mice. In Morris water maze. however. the ${\mu}$-opioid receptor knockout mice showed significant memory deficit compared to wild type mice. (omitted)

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.100-100
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• 1995

Several behavioral studies have suggested that ginseng total saponin (GTS) antagonizes morphine actions. Based on these observations, we conducted biochemical studies to elucidate the cellular mechanism of GTS actions. morphine hydrochloride (10mg/kg, sc) and/or on (400mg/kg, oral ) were administered to mice for 14 consecutive days. Ligand binding studies were conducted from striatal membranes. For opioid receptors, morphine increased the affinity but decreased the maximal binding sites for $^3$H naloxone. GTS partially recovered it. In case of dopamine receptors, morphine increased affinity and maximal binding sites for 3H spiperone. and GTS partially blocked it. These results suggest that morphine affects cellular events by modulating opioid receptors and that opioid receptors interact with dopamine receptors to change the mental status. GTS could be helpful for the treatment of morphine- induced mental disorders.

• Biomolecules & Therapeutics
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• v.5 no.1
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• pp.53-58
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• 1997

$[Lys^7$]dermorphin, abbreviated K7DA, which has structural features similar to a metabolically stable $\mu$-opioid peptide agonist $[D-Arg^2, Lys^4$]dermorphin analogue (DALDA), but is intrinsically more potent with respect to binding to the $\mu$-opioid peptide receptor. The present studies report on attempts to enhance brain uptake of systemically administered K7DA by conjugation to a complex of streptavidin (SA) and the OX26 murine monoclonal antibody to the rat transferrin receptor, which undergoes receptor-mediated transcytosis through the blood-brain barrier (BBB). SA-OX26 conjugate mediates BBB transport of biotinylated therapeutics. The K7DA is monobiotinylated at the $\varepsilon$-amino group of the $[Lys^7$] residue with cleavable linker using NHS-SS-biotin. The brain uptake of $^{125}I$ labeled biotinylated K7DA ($^{125}I$-bio-SSa-K7DA) was very small and rapidly metabolized after intravenous injection. The brain uptake, expressed as percent of injected dose delivered per gram of brain, of the $^{125}I$-bio-55-K7DA bound to the SA-OX26 conjugate $^{125}I$-bio-SS-K7DA/SA-OX26) was 0.14$\pm$0.01, a level that is 2-fold greater than the brain uptake of morphine. The cleavability of the disulfide linker in vivo in rat plasma and brain was assessed with gel filtration HPLC and intravenous injection of labeled opioid chimeric peptides. The disulfide linker is stable in plasma in vivo but is cleaved in rat brain in vivo. In conclusion, these studies show that delivery of these potential opioid peptides to the brain may be improved by coupling them to vector-mediated BBB drug delivery system.

• The Korean Journal of Pharmacology
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• v.24 no.2
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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.

• Korean Journal of Clinical Pharmacy
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• v.25 no.3
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• pp.145-150
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• 2015

Objective: Pain is very common in the elderly, so there is a high prevalence of analgesic use among this population. The purpose of this study was to assess patterns of analgesic use and evaluate factors associated with analgesic use in elderly patients. Method: The subjects of this study were patients over 65 years old hospitalized in a teaching hospital located in Chuncheon-si, Korea between January 1, 2014 and March 31, 2014. Data collection regarding analgesic prescriptions and baseline characteristics was conducted using computerized hospital database by medical information team. Logistic regression analysis was used to identify factors related to analgesic use. Results: A total of 2,394 patients were finally included. Among these patients, 700 (29.2%) took analgesics; 521 (74.4%) out of these 700 patients were received opioid analgesics and 179 (25.6%) were received only non-opioid analgesics. The most frequently prescribed opioid analgesic was pethidine (45.7%), and the most frequently prescribed non-opioid analgesic was acetaminophen (44.1%). Fracture was associated with increased odds of opioid analgesic prescriptions (OR = 2.766, 95% CI = 2.019-3.790, p < 0.001) and any analgesic prescriptions (OR = 2.394, 95% CI = 1.766-3.244, p < 0.001). Stroke or cerebral infarction was associated with decreased odds of opioid analgesic prescriptions (OR = 0.636, 95% CI = 0.471-0.858, p = 0.003). Conclusion: A significant proportion of hospitalized elderly patients use analgesics. Health care professionals should consider factors associated with analgesic use in this population to improve pain management.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.713-716
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• 2013

Social and behavioral scientists have proposed that a person's belief system crucially influences his or her behaviour, and therefore may affect outcomes of pain management. The purpose of this study was to explore the relationship between analgesic beliefs, analgesic adherence and pain experience amongst Taiwanese cancer outpatients. The cross-sectional study included 92 oncology outpatients in two teaching hospitals in the Taipei area of Taiwan. The research instruments included the Pain Opioid Analgesic Beliefs Scale-Cancer (POABS-CA), opioid adherence, and the Brief Pain Inventory-Chinese (BPI-Chinese). Beliefs about pain and opioids demonstrated a significant relationship with patients' opioid adherence (r = -0.30, p < 0.01). The more negative beliefs regarding opioids and pain the patient had, the worse their adherence to around the clock (ATC) analgesic regimen. However, there was no significant correlation between opioid belief and pain experience. As well, there were no significant relationships between adherence to opioid regimen and any of the measures of pain experience. The study highlights the potential importance of a patient's pain and opioid beliefs in adherence to pain medication.

• The Korean Journal of Pain
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• v.32 no.2
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• pp.79-86
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• 2019

Background: The use of aroma oils dates back to at least 3000 B.C., where it was applied to mummify corpses and treat the wounds of soldiers. Since the 1920s, the term "aromatherapy" has been used for fragrance therapy with essential oils. The purpose of this study was to determine whether the essential oil of Eucalyptus (EOE) affects pain pathways in various pain conditions and motor coordination. Methods: Mice were subjected to inhalation or intraperitoneal injection of EOE, and its analgesic effects were assessed by conducting formalin, thermal plantar, and acetic acid tests; the effects of EOE on motor coordination were evaluated using a rotarod test. To determine the analgesic mechanism, 5'-guanidinonaltrindole (${\kappa}$-opioid antagonist, 0.3 mg/kg), naltrindole (${\delta}$-opioid antagonist, 5 mg/kg), glibenclamide (${\delta}$-opioid antagonist, 2 mg/kg), and naloxone (${\mu}$-opioid antagonist, 4, 8, 12 mg/kg) were injected intraperitoneally. Results: EOE showed an analgesic effect against visceral pain caused by acetic acid (EOE, 45 mg/kg); however, no analgesic effect was observed against thermal nociceptive pain. Moreover, it was demonstrated that EOE did not have an effect on motor coordination. In addition, an anti-inflammatory effect was observed during the formalin test. Conclusions: EOE, which is associated with the ${\mu}$-opioid pain pathway, showed potential effects against somatic, inflammatory, and visceral pain and could be a potential therapeutic agent for pain.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9301-9305
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• 2014

Background: Pain is one of the most terrifying symptoms for cancer patients. Although most patients with cancer pain need opioids, complete relief of pain is hard to achieve. This study investigated the factors influencing persistent pain-free survival (PPFS) and opioid efficiency. Materials and Methods: A prospective study was conducted on 100 patients with cancer pain, hospitalized at the medical oncology clinic of Akdeniz University. Patient records were collected including patient demographics, the disease, treatment characteristics, and details of opioid usage. Pain intensity was measured using a patient self-reported visual analogue scale (VAS). The area under the curve (AUC) reflecting the pain load was calculated from daily VAS tables. PPFS, the primary measure of opioid efficacy, was described as the duration for which a patient reported a greater than or equal to two-point decline in their VAS for pain. Predictors of opioid efficacy were analysed using a multivariate analysis. Results: In the multivariate analysis, PPFS was associated with the AUC for pain (Exp (B)=0.39 (0.23-0.67), P=0.001), the cumulative opioid dosage used during hospitalisation (Exp (B)=1.00(0.99-1.00), P=0.003) and changes in the opioid dosage (Exp (B)=1.01 (1.00-1.01), P=0.016). The change in VAS score over the standard dosage of opioids was strongly associated with current cancer treatment (chemotherapy vs. others) (${\beta}=-0.31$, T=-2.81, P=0.007) and the VAS for pain at the time of hospitalisation (${\beta}=-0.34$, T=-3.07, P= 0.003). Conclusions: The pain load, opioid dosage, concurrent usage of chemotherapy and initial pain intensity correlate with the benefit received from opioids in cancer patients.