• The Korean Journal of Pain
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• v.35 no.1
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• pp.33-42
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• 2022

Background: Cupressus arizonica Greene is a coniferous tree with great importance in fragrance and pharmaceutical industries. Essential oils from C. arizonica (EC) have shown potential antioxidant, and anti-microbial activities. This study aimed at investigating the anti-nociceptive and anti-inflammatory effects/mechanisms of EC. Methods: The EC was evaluated for anti-nociceptive and anti-inflammatory activities on male Wistar rats using a formalin test and carrageenan-induced paw edema, respectively. Also, we pre-treated some of the animals with naloxone and flumazenil in the formalin test to find out the possible contributions of opioid and benzodiazepine receptors to EC anti-nociceptive effects. Finally, gas chromatography/mass spectrometry (GC/MS) analysis was used to identify the EC's constituents. Results: EC in intraperitoneal doses of 0.5 and 1 g/kg significantly decrease the nociceptive responses in both early and late phases of the formalin test. From a mechanistic point of view, flumazenil administration 20 minutes before the most effective dose of EC (1 g/kg) showed a meaningful reduction in the associated anti-nociceptive responses during the early and late phases of the formalin test. Naloxone also reduced the anti-nociceptive role of EC in the late phase. Furthermore, EC at the doses of 1, 0.5, and 0.25 g/kg significantly reduced paw edema from 0.5 hours after carrageenan injection to 4 hours. GC/MS analysis showed that isolated EC is a monoterpene-rich oil with the major presence of α-pinene (71.92%), myrcene (6.37%), δ-3-carene (4.68%), β-pinene (3.71%), and limonene (3.34%). Conclusions: EC showed potent anti-nociceptive and anti-inflammatory activities with the relative involvement of opioid and benzodiazepine receptors.

• The Korean Journal of Pain
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• v.31 no.2
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• pp.73-79
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• 2018

All drugs have both favorable therapeutic and untoward adverse effects. Conventional opioid analgesics possess both analgesia and adverse reactions, such as nausea, vomiting, and respiratory depression. The opioid ligand binds to ${\mu}$ opioid receptor and non-selectively activates two intracellular signaling pathways: the G protein pathway induce analgesia, while the ${\beta}$-arrestin pathway is responsible for the opioid-related adverse reactions. An ideal opioid should activate the G protein pathway while deactivating the ${\beta}$-arrestin pathway. Oliceridine (TRV130) has a novel characteristic mechanism on the action of the ${\mu}$ receptor G protein pathway selective (${\mu}$-GPS) modulation. Even though adverse reactions (ADRs) are significantly attenuated, while the analgesic effect is augmented, the some residual ADRs persist. Consequently, a G protein biased ${\mu}$ opioid ligand, oliceridine, improves the therapeutic index owing to increased analgesia with decreased adverse events. This review article provides a brief history, mechanism of action, pharmacokinetics, pharmacodynamics, and ADRs of oliceridine.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.16 no.8
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• pp.5336-5342
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• 2015

Although demand for scar treatment has been rising as our quality of life is improved, most scar treatment products rely on importation. Enkephalin is one of the neuropeptides secreted from neuronal ends. As both skin and neuron are derived from the exoderm during the development process, skin cells express opioid receptors as neuronal cells do. Opioid receptors are categorized into three types, mu(m)-, delta(d)-, and kappa(k)- opioid receptors, all of which are directly involved in the wound healing process. In this study, enkephalin derivatives are synthesized by Alanin Scan and their efficacy was evaluated and compared. In vitro wound healing effects, stimulatory effects of collagen synthesis, and skin hydration effects were also evaluated and confirmed. Among Enkephalin derivatives, AS13 showed highest wound healing effect.

• The Korean Journal of Pharmacology
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• v.30 no.2
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• pp.153-165
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• 1994

In this study, we tested the influences of several ${\kappa}$ opioid ligands on the $[^3H]diprenorphine$ binding in rat and guinea pig cortex membrane preparations. Using paradigm to block ${\mu}\;and\;{\delta}$ opioid receptors with $DAMGO(1{\mu}M)$ and $DPDPE(1{\mu}M)$, $[^3H]diprenorphine$ labeled ${\kappa}$ sites. Competition analysis in both rat and guinea pig cortex has shown a single population of $[^3H]diprenorphine$ binding site with different Kd values, respectively. There is a significant difference in Ki values of (-) WIN44441 and (+)WIN44441 in both rat and guinea pig cortex. Bremazocine, (-)ethylketocyclazocine, (-)cyclazocine, nor-binaltorphimine effectively inhibited the $[^3H]diprenorphine$ binding with different Ki values in rat and guinea pig cortex. U-69,593, U-50,488H and dynorphine-A (1-8) did not inhibit the $[^3H]diprenorphine$ binding in rat but in guinea pig cortex. Nor-binaltorphimine was a ligand discriminate the ${\kappa}_1$, and ${\kappa}_2$ receptor most effectively. We, also, examined the influence of Na ion and $GTP{\gamma}S$, a nonhydrolyzable guanine nucleotide analog, on the inhibition of $[^3H]diprenorphine$ binding by diprenorphine, (-)ethyl-ketocyclazocine, U-69,593 and bremazocine. By the replacement of NaCl with N-methy-D-glucamine or addition of $GTP{\gamma}S$, Ki values of diprenorpnine were not changed and that of ethylketocyclazocine were changed significantly in both rat and guinea pig cortex. The Ki value of bremazocine was decreased by removal of Na ion, and increased by $GTP{\gamma}S$, however, was not changed by any one of either. These results suggest that there are 2 kinds of subtypes of ${\kappa}$ opioid receptor, ${\kappa}_1$, and ${\kappa}_2$, showing different Ki values for various ${\kappa}$ opioid ligands, also, bremazocine possess the antagonistic property at ${\kappa}_2$ site which is dominant subtype of K receptor in rat cortex.

• Natural Product Sciences
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• v.17 no.4
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• pp.303-308
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• 2011

Spirodela polyrrhiza L. Schleid. (Lemnaceae), also known as 'duckweed', is a traditional medicine in Korea. The whole plant is used to treat many diseases, including the common cold, edema, acute nephritis, and urticaria. The present study investigated antinociceptive properties of the EtOAc soluble fraction of S. polyrrhiza (ESP). The antinociceptive activities of ESP were studied using experimental models of pain, including thermal nociception methods, such as the tail immersion test and the hotplate test. Moreover, we studied chemical nociception induced by intraperitoneal acetic acid and subplantar formalin in mice. ESP exhibited dose-dependent antinociceptive activity in both thermal and chemical pain models. In a drug combination test using the opioid receptor antagonist naloxone, diminished analgesic activities of ESP were observed, indicating that the antinociceptive activity of ESP is mediated by opioid receptors.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.130.2-130.2
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• 2003

The present study was undertaken to examine the hypothesis that $\mu$-opioid receptors play a crucial role in behavioral sensitization to nicotine using $\mu$-opioid receptor knockout mice. All mice were treated acutely or repeatedly with nicotine 0.05 mg/kg twice daily for 7 consecutive days. The mice were challenged with nicotine on day 11. And locomotor activity was measured for 30min. (omitted)

• Advances in Traditional Medicine
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• v.6 no.3
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• pp.186-195
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• 2006

The present study was carried out to determine the involvement of opioid and non-opioid receptor and the effect of pH and enzymes on the recently reported antinociceptive activity of aqueous extract of Corchorus olitorius (AECO) leaves using the abdominal constriction test. The extract was prepared by soaking the dried powdered leaves of Corchorus (C.) olitorius in distilled water overnight, and the supernatant obtained was considered as a stock solution with 100% concentration/ strength. The extract, administered subcutaneously in the concentrations/ strength of 10, 50 and 100%, was found to show a significant concentration-independent antinociception. The 50% concentration AECO were further used to study on the above mentioned parameters. The extract exhibited: significant (P < 0.05) decreased in activity when pre-treated (s.c.) against 10 mg/kg naloxonazine, bicuculine (10 mg/kg), phenoxybenzamine (10 mg/kg), 10 mg/kg pindolol, and 5 mg/kg mecamylamme, but not 10 mg/kg naltrindole, 10 mg/kg atropine, respectively; significant (P < 0.05) decreased in activity after pre-treatment against 10% a-amylase, but not 1 % protease or 10% lipase and; significant (P < 0.05) decreased in activity after exposure to alkaline condition (pH between 9 and 13) while maintaining the activity at acidic condition, respectively. The C. olitorius leaves antinociception, which involved, at least in part, activation of $\mu-opioid,\;\alpha-and\;\beta-adrenergic$, and nicotinic receptors, was found to decrease under alkaline condition and in the presence of $\alpha-amylase$.

• The Korean Journal of Pain
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• v.23 no.4
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• pp.236-241
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• 2010

Background: Selective inhibitors of cycloosygenase (COX)-2 are commonly used analgesics in various pain conditions. Although their actions are largely thought to be mediated by the blockade of prostaglandin (PG) biosynthesis, evidences suggesting endogenous opioid peptide link in spinal antinociception of COX inhibitor have been reported. We investigated the roles of opioid receptor subtypes in the spinal antionociception of selective COX-2 inhibitor. Methods: To examine the antionociception of a selective COX-2 inhibitor, DUP-697 was delivered through an intrathecal catheter, 10 minutes before the formalin test in male Sprague-Dawley rats. Then, the effect of intrathecal pretreatment with CTOP, naltrindole and GNTI, which are ${\mu}$, $\delta$, and k opioid receptor antagonist, respectively, on the analgesia induced by DUP-697 was assessed. Results: Intrathecal DUP-697 reduced the flinching response evoked by formalin injection during phase 1 and 2 Naltrindole and GNTI attenuated the antinociceptive effect of intrathecal DUP-697 during both phases of the formalin test, CTOP reversed the antinociception of DUP-697 during phase 2, but not during phase 1, Conclusions: Intrathecal DUP-697, a selective COX-2 inhibitor, effectively relieved inflammatory pain in rats. The $\delta$ and $\kappa$ opioid receptors are involved in the activity of COX-2 inhibitor on the facilitated state as well as acute pain at the spinal level, whereas the ${\mu}$ opioid receptor is related only to facilitated pain.

• The Korean Journal of Pain
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• v.18 no.1
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• pp.1-9
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• 2005

Background: Spinal metabotropic glutamate receptors (mGluRs) and opioid receptors are involved in the modulation of nociception. Although opioid receptors agonists are active for pain, the effects of the compounds for the mGluRs have not been definitely investigated at the spinal level. We examined the effects of the intrathecal mGluR compounds and morphine in the nociceptive test, and then we further clarified the role of the spinal mGluRs. In addition, the nature of the pharmacological interaction after the coadministration of mGluRs compounds with morphine was determined. Methods: Catheters were inserted into the intrathecal space of male SD rats. For the induction of pain, $50{\mu}l$ of 5% formalin solution or a thermal stimulus was applied to the hindpaw. An isobolographic analysis was used for the evaluation of the drug interaction. Results: Neither group I mGluR compounds nor group III mGluR compounds produced any antinociceptive effect in the formalin test. The group II mGluR agonist (APDC) had little effect on the formalin-induced nociception. The group II mGluR antagonist (LY 341495) caused a dose-dependent suppression of the phase 2 flinching response on the formalin test, but it did not reduce the phase 1 response of the formalin test nor did it increase the withdrawal latency of the thermal stimulus. Isobolographic analysis revealed a synergistic interaction after the intrathecal delivery of a LY 341495-morphine mixture. Conclusions: These results suggest that group II mGluRs are involved in the facilitated processing at the spinal level, and the combination of LY 341495 with morphine may be useful to manage the facilitated pain state.

• International Journal of Oral Biology
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• v.34 no.3
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• pp.137-142
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• 2009

Whole-body $\gamma$-irradiation(WBI), which produces an oxidative stress, is reported to attenuate the acute antinociceptive action of morphine (a $\mu$-opioid receptor agonist), but not DPLPE (a $\delta$-opioid receptor agonist), in mice. Recently, we also reported that antinociceptive effect of morphine, but not $\beta$-endorphin (a novel $\varepsilon$-opioid receptor agonist), was attenuated by oxidative stress. These findings prompted us to investigate the effect of WBI on the antinociception of morphine and $\beta$-endorphin in mice. Mice were exposed to WBI (5 Gy) from a $^{60}Co$ gamma-source and tested 2 hours later for antinociception produced by intracerebroventricular administration of morphine or $\beta$-endorphin using the hot water tail-immersion and the writhing tests. WBI significantly attenuated the antinociception produced by morphine only in the hot water tail-immersion test, whereas the antinociception of $\beta$-endorphin was significantly potentiated by WBI in both tests. These results demonstrate a differential sensitivity of $\mu$- and $\varepsilon$-opioid receptors to WBI, and support the hypothesis that morphine and $\beta$-endorphin administered supraspinally produce antinociception by different neuronal mechanisms.