• Korean Journal of Pharmacognosy
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• v.47 no.1
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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.

• 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.

• The Korean Journal of Pain
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• v.26 no.3
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• pp.223-241
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• 2013

Boney metastasis may lead to terrible suffering from debilitating pain. The most likely malignancies that spread to bone are prostate, breast, and lung. Painful osseous metastases are typically associated with multiple episodes of breakthrough pain which may occur with activities of daily living, weight bearing, lifting, coughing, and sneezing. Almost half of these breakthrough pain episodes are rapid in onset and short in duration and 44% of episodes are unpredictable. Treatment strategies include: analgesic approaches with "triple opioid therapy", bisphosphonates, chemotherapeutic agents, hormonal therapy, interventional and surgical approaches, steroids, radiation (external beam radiation, radiopharmaceuticals), ablative techniques (radiofrequency ablation, cryoablation), and intrathecal analgesics.

• The Korean Journal of Pain
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• v.23 no.2
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• pp.99-108
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• 2010

Chronic pain is a multifactorial condition with both physical and psychological symptoms, and it affects around 20% of the population in the developed world. In spite of outstanding advances in pain management over the past decades, chronic pain remains a significant problem. This article provides a mechanism- and evidence-based approach to improve the outcome for pharmacologic management of chronic pain. The usual approach to treat mild to moderate pain is to start with a nonopioid analgesic. If this is inadequate, and if there is an element of sleep deprivation, then it is reasonable to add an antidepressant with analgesic qualities. If there is a component of neuropathic pain or fibromyalgia, then a trial with one of the gabapentinoids is appropriate. If these steps are inadequate, then an opioid analgesic may be added. For moderate to severe pain, one would initiate an earlier trial of a long term opioid. Skeletal muscle relaxants and topicals may also be appropriate as single agents or in combination. Meanwhile, the steps of pharmacologic treatments for neuropathic pain include (1) certain antidepressants (tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors), calcium channel ${\alpha}2-{\delta}$ ligands (gabapentin and pregabalin) and topical lidocaine, (2) opioid analgesics and tramadol (for first-line use in selected clinical circumstances) and (3) certain other antidepressant and antiepileptic medications (topical capsaicin, mexiletine, and N-methyl-d-aspartate receptor antagonists). It is essential to have a thorough understanding about the different pain mechanisms of chronic pain and evidence-based multi-mechanistic treatment. It is also essential to increase the individualization of treatment.

• Journal of Acupuncture Research
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• v.23 no.4
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• pp.149-162
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• 2006

Objectives : The aim of this study is to evaluate the analgesic effect of electroacupuncture on Jogsamni (ST36) in the collagen-induced arthritis rats and investigate the role played by opioid receptor subtypes $({\mu},\;{\delta},\;{\kappa})$ in the antinociceptive effect of electroacupuncture (EA) In the thermal hyper algesia test. Methods : Immunization of male Sprague-Dawley rats with bovine type H collagen emulsified in incomplete Freund's adjuvant, followed by booster injection 2 weeks later induced collagen-induced arthritis (CIA). The thermal hyperalgesia was evaluated weekly with tail flick latency (TFL). In the fourth week after first immunization, EA stimulation (2 Hz, 0.07 mA, 0.3 ms) was delivered into Jogsamni (5736) for 20 minutes. Analgesic effect was evaluated by using the tail flick latency (TFL) after intraperitoneal injection of normal saline, naloxone, naltrindole and nor-binaltorphimine respectively to CIA rats. Results : The results were as follows; 1. The TFL were gradually decreased in CIA as time elapsed after e immunization of arthrogenic collagen and the maximum value was reached between the third to fifth week. 2. EA stimulation on 5736 inhibited chronic inflammatory pain induced by CIA. 3. The analgesic effect of EA was inhibited by pretreatment of ${\mu}-receptor$ antagonist (naloxone),${\delta}-receptor$ antagonist (naltrindole) and ${\kappa}-receptor$ antagonist (nor-binaltorphimine) respectively. Conclusion : Electroacupuncture has an analgesic effect on the CIA rat and has an antinociception mediated by 8, 5, H receptors.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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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 ${\mu}$.

• BMB Reports
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• v.35 no.4
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• pp.420-427
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• 2002

Partial nerve injury is the main cause of neuropathic pain disorders in humans. Acupuncture has long been used to relieve pain. It is known to relieve pain by controlling the activities of the autonomic nervous system. Although the mechanism of neuropathic pain and analgesic effects of electroacupuncture (EA) have been studied in a rat model system, its detailed mechanism at the molecular level remains unclear. To identify genes that might serve as either markers or explain these distinct biological functions, a cDNA microarray analysis was used to compare the expression of 8,400 genes among three sample groups. Messenger RNAs that were pooled from the spinal nerves of 7 normal. 7 neuropathic pain, and 7 EA treatment rat models were compared. Sixty-eight genes were differentially expressed more than 2-fold in the neuropathic rat model when compared to the normal, and restored to the normal expression level after the EA treatment. These genes are involved in a number of biological processes, including the signal transduction, gene expression, and nociceptive pathways. Confirmation of the differential gene expression was performed by a dot-blot analysis. Dot-blotting results showed that the opioid receptor sigma was among those genes. This indicates that opioid-signaling events are involved in neuropathic pain and the analgesic effects of EA. The potential application of these data include the identification and characterization of signaling pathways that are involved in the EA treatment, studies on the role of the opioid receptor in neuropathic pain, and further exploration on the role of selected identified genes in animal models.

• 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.

• Biomolecules & Therapeutics
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• v.12 no.4
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• pp.198-201
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• 2004

This review focuses on finding neurochemical changes in physical dependence on butorphanol, a relatively potent mixed agonist-antagonist opioid analgesic agent that is five times more potent than morphine in antinociceptive effects. The chronic administration of butorphanol induces physical dependence. Withdrawal from such dependence can be reliably precipitated by administration of a narcotic antagonist, e.g., naloxone. Evidence for critical involvement of excitatory aminoacid (glutamate), opioid receptors, and phosphorylation of proteins in these phenomena is summarized.

• The Korean Journal of Pain
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• v.13 no.1
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• pp.49-54
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• 2000

Background: Evidence has accumulated that opioids can produce potent antinociceptive effects by interacting with opioid receptors in peripheral tissues. Bupivacaine has a potent analgesic effect with early peak onset in the postoperative period. The combination of intrapelvic bupivacaine and morphine has been suggested as an ideal analgesic after endoscopic pelvic surgery. Methods: Sixty patients scheduled for endoscopic pelvic surgery under general anesthesia were allocated randomly to three groups. Group 1 received normal saline 20 ml, group 2 received morphine 5 mg in normal saline 20 ml, and group 3 received morphine 5 mg in 0.25% bupivacaine 20 ml into the pelvic cavity. Postoperative pain was assessed using the visual analogue scale at 1, 2, 4, 8, and 24 hours after the intrapelvic instillation. Supplemental analgesic requirements, vital signs, and side effects were recorded for 24 hours. Results: Intrapelvic morphine and bupivacaine produced significant analgesia after endoscopic pelvic surgery. The patients in group 3 had lower pain scores than those in the group 1 and 2 at 1, 2 and 4th hours. There were no significant differences in the pain scores at 8 hours and 24 hours postoperatively between group 2 and 3. Supplemental analgesic requirements were significantly greater in the groups 1 and 2 than the group 3 for 24 hours. No significant side effects occurred. Conclusion: The intrapelvic instillation of morphine and bupivacaine is effective for the postoperative pain control in patients undergoing endoscopic pelvic surgery.