• Journal of Ginseng Research
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• v.14 no.2
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• pp.178-186
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• 1990

The analgesic effect of morphine was antagonized and the development of tolerance was suppressed by the modification of the neurologic function in the animals treated with ginseng saponins The activation of the spinal descending inhibitory systems as well as the supraspinal structures by the administration of morphine was inhibited in the animals treated with ginseng saponine intracerebrally or intrathecally. The development of morphine tolerance and dependence, and the abrupt expression of naloxone inducted abstinence syndrom were also inhibited by ginsenoside Rb1, Rb2, Rg1 and Re. These results suggest that ginsenoside Rbl, Hbs, Rgl and Re are the bioactive components of panax ginseng on the inhibition of the development of morphine tolerance and dependence, and the inhibition of abrupt abstinence sindrome. In addition, further research on the minor components of Pnnnxkinsenl should be investigated. A single or daily treatment with ginseng saponins did not induce any appreciable changes in the brain in level of monoamines at the variolls time intervals and at the various day intervals, respectively. The inhibitory or facilitated effects of ginseng saponins on electrically evoked contractions in guinea pig ileum ($\mu$-receptor) and mouse vats deferens ($\delta$-receptor) were not mediated through opioid receptors. The antagonism of a $\chi$ receptor agonist, U-50, 488H was also not mediated through opioid receptors in the animals treated with ginseng saponins, but mediated through serotonergic mechanisms. Ginseng saponins inhibited morphine 6-dehydrogenase which catalyzed the production of morphinone from morphine, and increased hepatic glutathione contents for the detoxication of morphinone. This result suggests that the dual action of the above plays an important role in the inhibition of the development of morphine tolerance and dependence.

• The Korean Journal of Pain
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• v.18 no.2
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• pp.99-106
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• 2005

Background: Cyclic guanosine monophosphate (cGMP) and opioid receptors are involved in the modulation of nociception. Although the opioid receptors agonists are active in pain, the effect of an phospodiesterase inhibitor (zaprinast) for increasing the level of cGMP has not been thoroughly investigated at the spinal level. This study examined the effects of intrathecal zaprinast and morphine in a nociceptive test and we also examined the nature of the pharmacological interaction after the coadministration of zaprinast with morphine. The role of the nitric oxide (NO)-cGMP-potassium channel pathway on the effect of zaprinast was further clarified. Methods: Catheters were inserted into the intrathecal space of male SD rats. For the induction of pain, $50{\mu}l$ of 5% formalin solution was applied to the hindpaw. Isobolographic analysis was used for the evaluation of the drug interaction between zaprinast and morphine. Furthermore, NO synthase inhibitor ($_L-NMMA$), guanylyl cyclase inhibitor (ODQ) or a potassium channel blocker (glibenclamide) were intrathecally administered to verify the involvement of the NO-cGMP- potassium channel pathway on the antinociception effect of zaprinast. Results: Both zaprinast and morphine produced an antinociceptive effect during phase 1 and phase 2 in the formalin test. Isobolographic analysis revealed a synergistic interaction after the intrathecal administration of the zaprinast-morphine mixture in both phases. Intrathecal $_L-NMMA$, ODQ and glibenclamide did not reverse the antinociception of zaprinast in either phase. Conclusions: These results suggest that zaprinast, morphine and the mixture of the two drugs are effective against acute pain and they facilitated pain state at the spinal level. Thus, the spinal combination of zaprinast with morphine may be useful for the management of pain. However, the NO-sensitive cGMP-potassium channel pathway did not contribute to the antinocieptive mechanism of zaprinast in the spinal cord.

• The Journal of Korean Medicine
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• v.41 no.4
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• pp.88-99
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• 2020

Objectives: The purpose of this study is to investigate the mechanism of acupuncture for treating chemotherapy-induced peripheral neuropathy. Methods: Based on domestic and international papers reported until October 2020, experimental papers on "chemotherapy induced peripheral neuropathy", "mechanism", and "acupuncture" were set up to identify the mechanisms of chemotherapy induced peripheral neuropathy. A total of seven papers were selected and searched: one pilot paper for people and six experimental papers for rats. Results: In the pilot paper studied by Bao, T., the effect of EA was demonstrated but no significant results were produced for the mechanism. Moon et al. derived the association between EA and plasma 𝛽-endorphin in rat experimental studies on oxalilatin-induced cold hypersensitivity. Meng et al. found relevance to 𝜇, 𝛿, and 𝛿 opioid through EA stimulation in paclitaxel-induced peripheral neuropathy. Lee et al. studied the relationship between EA and muscarin and 5-HT in rat experiments on oxaliplatin-induced coldness, associated with 5-HT and EA, especially with 5-HT3 receptors. Choi et al. revealed the association of adrenaline and opioid acting on 𝛼2- and 𝛽 adrenaline receptors with EA in rat experiments on paclitaxel-induced neuralgia. In rat experiments on oxaliplatin-induced neuralgia reported by Lee, 𝛽-endorphin and encephalin were studied to be mediated by EA. Zhang, T. et al. revealed in the paclitaxel induced rat experiment that EA activates 5-HT. Conclusion: It is inferred that peripheral neuropathy caused by anticancer drugs can be reduced by activating the action of 5-HT, 𝛽-endorphin, and encephalin through the descending inhibitory pathways. cell differentiation, herbal medicine, Pongamia, stem cells

• The Korean Journal of Pain
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• v.37 no.1
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• pp.26-33
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• 2024

Background: Sitagliptin is an antidiabetic drug that inhibits dipeptidyl peptidase-4 enzyme. This study aimed to investigate the antinociceptive and anti-inflammatory effects of sitagliptin in formalin and carrageenan tests and determine the possible mechanism(s) of its antinociceptive activity. Methods: Male Swiss mice (25-30 g) and male Wistar rats (180-220 g) were used for formalin and carrageenan tests, respectively. In the formalin test, paw licking time and in the carrageenan test, paw thickness were considered as indexes of pain behavior and inflammation respectively. Three doses of sitagliptin (2.5, 5, and 10 mg/kg) were used in these tests. Also, several antagonists and enzyme inhibitors were used to evaluate the role of adrenergic, serotonergic, dopaminergic, and opioid receptors as well as the NO/cGMP/K_ATP pathway in the antinociceptive effect of sitagliptin (5 mg/kg). Results: Sitagliptin showed significant antinociceptive and anti-inflammatory effects in the formalin and carrageenan tests respectively. In the carrageenan test, all three doses of sitagliptin significantly (P < 0.001) reduced paw thickness. Pretreatment with yohimbine, prazosin, propranolol, naloxone, and cyproheptadine could not reverse the antinociceptive effect of sitagliptin (5 mg/Kg), which indicates that adrenergic, opioid, and serotonin receptors (5HT₂) are not involved in the antinociceptive effects. L-NAME, methylene blue, glibenclamide, ondansetron, and sulpiride were able to reverse this effect. Conclusions: NO/cGMP/K_ATP, 5HT₃ and D₂ pathways play an important role in the antinociceptive effect of sitagliptin. Additionally significant anti-inflammatory effects observed in the carrageenan test might contribute in reduction of pain response in the second phase of the formalin test.

• The Korean Journal of Pharmacology
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• v.30 no.3
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• pp.299-311
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• 1994

The present study was attempted to investigate whether pentazocine, which is known to possess both opioid agonistic and antagonistic properties, produces catecholamines (CA) secretion from the isolated perfused rat adrenal gland, and to establish the mechanism of its action, and also to compare its action with that of some opioids. Pentazocine (30 to 300 ug) injected into an adrenal vein caused a dose-dependent secretory response of CA from the rat adrenal medulla. The pentazocine-evoked secretion of CA was remarkably diminished by the preloading with chlorisondamine $(10^{-6}\;M)$, naloxone $(1.22{\times}10^{-7}\;M)$, morphine $(1.7{\times}10^{-5}\;M)$, met-enkephalin $(9.68{\times}10^{-6}\;M)$, nicardipine $(10^{-6}\;M)$ and TMB-8 $(10^{-5}\;M)$ while was not influenced by the pretreatment of pirenzepine $(2{\times}10^{-6}\;M)$. The perfusion of $Ca^{++}$-free Krebs solution for 30 min into the gland also led to the marked reduction in CA secretion evoked by pentazocine. Furthermore, the CA release evoked by ACh and/or DMPP was greatly inhibited by the pretreatment with pentazocine $(1.75{\times}10^{-4}\;M)$ for 20 min. From these experimental results, it is thought that pentazocine causes markedly the increased secretion of CA from the isolated perfused rat adrenal medulla by a calcium-dependent exocytotic mechanism. The secretory effect of pentazocine appears to be mediated through activation of opioid receptors located on adrenal chromaffin cells, which may be also associated with stimulation of cholinergic nicotinic receptors.

• Journal of Dairy Science and Biotechnology
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• v.26 no.1
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• pp.11-19
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• 2008

Milk from dairy cows has long provided a high quality source of protein and selected micronutrients as calcuim to most populations. Recently, a relationship between disease risk and consumption of specific bovine ${\beta}$-casein fraction either A1 or A2 genetic variants has identified. Populations, which consume milk contain high containing high levels of ${\beta}$-casein A2 variants, have a lower incidence of cardiovascular disease and type 1 diabetes. Furthermore, consumption of milk with the A2 variants may be associated with less severe symptoms of autism and schizophrenia. The mechanism of action focuses on ${\beta}$-casein A1 and related forms preferentially that are able to produce a bioactive opioid peptide, ${\beta}$-casomorphin-7(${\beta}$-CM-7) during digestion. Infants may absorb ${\beta}$-CM-7 due to an immature gastrointestinal tract. Adult, on the other hand, appear to reap the biological activity locally on the intestinal brush boarder. ${\beta}$-CM-7 can potentially affect numerous opioid receptors in the nervous, endocrine, and immune system. Whether there is a definite health benefit to milk containing the A2 genetic variant is unknown and requires further investigation.

• Journal of Ginseng Research
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• v.13 no.2
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• pp.239-241
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• 1989

Naloxone partially antagonized the analgesic effect of a large dose of morphine and inhibited the development of an acute type tolerance. Ginseng total saponins did not antagonize the analgesia of a large dose of morphine but inhibited the delrelopment of acute and delayed types tolerance. The morphine analgesia and the development of acute type tolerance were affected by the opioid receptor antagonist, naloxone, but the development of acute type tolerance was not. Ginseng total saponins partially inhibited the development of the delayed type tolerance that was not inhibited by naloxone, but also partially suppressed the development of the acute type tolerance that was completely inhibited by naloxone. These results imply that the partial inhibition of the development of the acute and delayed types tolerance by ginseng total saponins is not mediated by the opioid receptors.

• The Korean Journal of Pain
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• v.2 no.2
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• pp.189-193
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• 1989

The analgesic effects of epidural morphine were evaluated on various types of cancer-related pain in forty-eight adult patients. Epidural morphine injections were given via an epidural catheter introduced to an epidural level corresponding to the pain area. Pain relief was classified as excellent, fair, or poor by subjective scoring and by the subsequent need for systemic analgesics. Thirty-two patients of all the patients became pain-free. In sixteen patients, pain relief was complete only for one or two of various types of pain with a certain dose of epidural morphine, The best result was obtained when the pain was continuous and originated from deep somatic structures. Based on the results, the ranking order of different types of cancer pain with regard to their susceptibility to epidural morphine was as follows: 1) Continuous somatic pain 2) Continuous visceral pain 3) Intermittent somatic pain 4) Intermittent visceral pain The differential effects of epidural morphine on cancer-related pain may suggest that various types of noxious stimuli involve different kinds of opioid receptors which differ in affinity to morphine, and that there are some pain-mediating systems which function independently of opioid mechanisms.

• International Journal of Oral Biology
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• v.35 no.2
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• pp.69-74
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• 2010

The mu opioid receptor (MOR) has been regarded as the main site of interaction with analgesics in major clinical use, particularly morphine. The repressor element-1 silencing transcription factor (REST) functions as a transcriptional repressor of neuronal genes in non-neuronal cells. However, it is expressed in certain mature neurons, suggesting that it may have complex and novel roles. In addition, the interactions between MOR and REST and their functions remain unclear. In this study, we examined the effects of morphine on the expression of REST mRNA and protein in human neuroblastoma NMB cells to investigate the roles of REST induced by MOR activation in neuronal cells. To determine the effects of morphine on REST expression, we performed RT-PCR, real-time quantitative RT-PCR, western blot analysis and radioligand binding assays in NMB cells. By RTPCR and real-time quantitative RT-PCR, the expression of REST was found to be unchanged by either the MOR agonist morphine or the MOR specific antagonist CTOP. By western blot, morphine was shown to significantly inhibit the expression of REST, but this suppression was completely blocked by treatment with CTOP. In the radioligand binding assay, the overexpression of REST led to an increased opioid ligand binding activity of endogenous MOR in the NMB cells. These results together suggest that morphine inhibits the expression of REST in human neuroblastoma cells through a post-transcriptional regulatory mechanism mediated through MOR.

• The Korean Journal of Pain
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• v.35 no.4
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• pp.423-432
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• 2022

Background: The decreased expression of mu-opioid receptors (MOR) in the amygdala may be a key molecular in chronic post-surgical pain (CPSP). It is known that miR-339-5p expression in the amygdala of a stressed rat model was increased. Analyzed by RNAhybrid, miR-339-5p could target opioid receptor mu 1 (oprm1) which codes MOR directly. So, the authors hypothesized that miR-339-5p could regulate the expression of MOR via targeting oprm1 and cause the effects to CPSP. Methods: To simulate perioperative short-term stress, a perioperative stress prolongs incision-induced pain hypersensitivity without changing basal pain perception rat model was built. A pmiR-RB-REPORT^TM dual luciferase assay was taken to verify whether miR-339-5p could act on oprm1 as a target. The serum glucocorticoid level of rats was test. Differential expressions of MOR, GFAP, and pERK1/2 in each group of the rats' amygdala were tested, and the expressions of miR-339-5p in each group of rats' amygdalas were also measured. Results: Perioperative stress prolonged the recovery time of incision pain. The expression of MOR was down-regulated in the amygdala of rats in stress + incision (S + IN) group significantly compared with other groups (P < 0.050). miR-339-5p was up-regulated in the amygdala of rats in group S + IN significantly compared with other groups (P < 0.050). miR-339-5p acts on oprm1 3'UTR and take MOR mRNA as a target. Conclusions: Perioperative stress could increase the expression of miR-339-5p, and miR-339-5p could cause the expression of MOR to decrease via targeting oprm1. This regulatory pathway maybe an important molecular mechanism of CPSP.