• The Korean Journal of Pain
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• v.22 no.1
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• pp.58-64
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• 2009

Background: Magnesium is a noncompetitive antagonist of the N-methyl-D aspartate (NMDA) receptor. Magnesium is thought to be involved in opioid tolerance by way of inhibiting calcium entry into cells. Methods: The patients were randomly assigned to three groups according to the anesthetic regimens: Group M received magnesium sulfate and Group C received saline intravenously under remifentanil-based anesthesia. Group S received saline intravenously under sevoflurane based anesthesia in place of remifentanil. The patients in the group M received 25% magnesium sulfate 50 mg/kg in 100 ml of saline, and those patients in groups C and S received an equal volume of saline before induction of anesthesia; this was followed by 10 mg/kg/h infusion of either magnesium sulfate (group M) or an equal volume of saline (groups C and S) until the end of surgery. Pain was assessed on a visual analog scale at 1, 6, 12, 24, and 36 hours after the operation. The time to the first postoperative analgesic requirement and the cumulative analgesic consumption were evaluated in the three groups. Results: The visual analog scales for pain and the cumulative analgesic consumption were significantly greater in group C than in other groups. The time to first postoperative analgesic requirement was significantly shorter in group C than that in the other groups. There were no differences between group M and S for side effects. Conclusions: A relatively high dose and continuous remifentanil infusion is associated with clinically relevant evidence of acute opioid tolerance. NMDA-receptor antagonist, magnesium sulfate as an adjuvant analgesic prevents opioid tolerance in patients who are undergoing major abdominal surgery under high dose and continuous remifentanil infusion-based anesthesia.

• The Korean Journal of Pain
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• v.27 no.3
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• pp.200-209
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• 2014

Background: Spinal opioid administration is an excellent option to separate the desirable analgesic effects of opioids from their expected dose-limiting side effects to improve postoperative analgesia. Therefore, physicians must better identify either specific opioids or adequate doses and routes of administration that result in a mainly spinal site of action rather than a cerebral analgesic one. Methods: The purpose of this topical review is to describe current available clinical evidence to determine what opioids reach high enough concentrations to produce spinally selective analgesia when given by epidural or intrathecal routes and also to make recommendations regarding their rational and safety use for the best management of postoperative pain. To this end, a search of Medline/Embase was conducted to identify all articles published up to December 2013 on this topic. Results: Recent advances in spinal opioid bioavailability, based on both animals and humans trials support the theory that spinal opioid bioavailability is inversely proportional to the drug lipid solubility, which is higher in hydrophilic opioids like morphine, diamorphine and hydromorphone than lipophilic ones like alfentanil, fentanyl and sufentanil. Conclusions: Results obtained from meta-analyses of RTCs is considered to be the 'highest' level and support their use. However, it's a fact that meta-analyses based on studies about treatment of postoperative pain should explore clinical surgery heterogeneity to improve patient's outcome. This observation forces physicians to use of a specific procedure surgical-based practical guideline. A vigilance protocol is also needed to achieve a good postoperative analgesia in terms of efficacy and security.

• The Korean Journal of Pain
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• v.37 no.3
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• pp.211-217
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• 2024

Background: Tolerance to the analgesic effects of opioids and non-steroidal anti-inflammatory drugs (NSAIDs) is a major concern for relieving pain. Thus, it is highly valuable to find new pharmacological strategies for prolonged therapeutic procedures. Biguanide-type drugs such as metformin (MET) are effective for neuroprotection and can be beneficial for addressing opioid tolerance in the treatment of chronic pain. It has been proposed that analgesic tolerance to NSAIDs is mediated by the endogenous opioid system. According to the cross-tolerance between NSAIDs, especially sodium salicylate (SS), and opiates, especially morphine, the objective of this study was to investigate whether MET administration can reduce tolerance to the anti-nociceptive effects of SS. Methods: Fifty-six male Wistar rats were used in this research (weight 200-250 g). For induction of tolerance, SS (300 mg/kg) was injected intraperitoneally for 7 days. During the examination period, animals received MET at doses of 50, 75, or 100 mg/kg for 7 days to evaluate the development of tolerance to the analgesic effect of SS. The hot plate test was used to evaluate the drugs' anti-nociceptive properties. Results: Salicylate injection significantly increased hot plate latency as compared to the control group, but the total analgesic effect of co-treatment with SS + Met50 was stronger than the SS group. Furthermore, the effect of this combination undergoes less analgesic tolerance over time. Conclusions: It can be concluded that MET can reduce the analgesic tolerance that is induced by repeated intraperitoneal injections of SS in Wister rats.

• Journal of Acupuncture Research
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• v.22 no.1
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• pp.99-108
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• 2005

Objective : The aim of this study is to investigate the analgesic effect and its mechanism of bee venom acupuncture on collagen-induced arthritis(CIA) rats. Methods : Bee venom (1 mg/kg) was subcutaneously punctured into Choksamni (ST36) of CIA Analgesic effect was evaluated by using the tail flick latency (TFL). Opioid and ${\alpha}2$-adrenergic neurotransmitter system were examined by naloxone as an opioid receptor antagonist and yohimbine as ${\alpha}2$-adrenoceptor antagonist prior to bee venom cupuncture. Results : The results were as follows; 1. The TFL for the CIA rat was decreased as time went by. 2. The TFL in CIA rat was increased in bee venom acupuncture group compared with control group (no treatment). 3. Analgesic effect of bee venom acupuncture was not abolished by naloxone pre-treatment in the CIA rat. 4. Analgesic effect of bee venom aqua-acupuncture was abolished by yohimbine pre-treatment in the CIA rat. 5. Two weeks bee venom acupuncture had the continous analgesic effect for 4 weeks. Conclusions : Bee venom acupuncture has an analgesic effect on the CIA rat and has an antinociception mediated by ${\alpha}2$-adrenergic system.

• Journal of Acupuncture Research
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• v.18 no.1
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• pp.76-87
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• 2001

Objective : Zusanli(ST36) and Hoku(Li4) are analgesic acupuncture points frequently used for acupuncture in Oriental medicine. The present study was conducted to see the antinociceptive effects produced by electroacupuncture combined two frequencies(Low, High) and two different acupuncture points(LI4, ST36) in the rat tail flick test. Method : In this study the Rats (Sprague-Dawley, 250-300g) were partially anesthetized with thiopental sodium(40mg/kg, i.p.). The basal reaction time for the tail-flick was 3${\pm}$0.5 sec. Low frequency(3Hz, 5V, biphasic) and high frequency(100Hz, 5V, biphasic) were applied to the inserted needle for the period of insertion(twenty minutes). Experimental groups are divied as follow; a) electroacupuncture stimulation groups at Hoku with or high frequency(L-EA, H-EA), b) electroacupuncture stimulation groups at Zusanli with low or high frequency(1-EA, h-EA), c) low frequency at Hoku and Zusanli(LIEA), d) low frequency at Hoku and high frequency at Zusanli(LhEA), e) high frequency at Hoku and low frequency at Zusanli(HIEA), f) high frequency at Hoku and Zusanli(HhEA) Results : The individual stimulation at either Hoku or Zusanli with low frequency has stronger and longer analgesic effect than high frequency stimulation. In addition, the combined stimulation at Hoku and Zusanli with low frequency has superior effect to individual stimulation with low frequency. LhEA and LIEA have superior effect to other stimulation groups among the combined groups. In order to determine the involvement of opioid system on the different antinociceptive effects, Naloxone, an opioid antagonist, was used in the combined groups. LIEA is the most sensitive when naloxone was administrated among study groups. HhEA is the least sensitive in the administration of naloxone. Conclusion : From results, this study confirmed that the opioid system is involved in analgesic effect of low frequency stimulation of acupuncture point, and we also can suggest the stronger analgesic effect of combining stimulation points is due to the theory of spatial summation in the nervous system.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.4
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• pp.419-425
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• 2018

The superficial dorsal horn of the spinal cord plays an important role in pain transmission and opioid activity. Several studies have demonstrated that opioids modulate pain transmission, and the activation of ${\mu}$-opioid receptors (MORs) by opioids contributes to analgesic effects in the spinal cord. However, the effect of the activation of MORs on GABAergic interneurons and the contribution to the analgesic effect are much less clear. In this study, using transgenic mice, which allow the identification of GABAergic interneurons, we investigated how the activation of MORs affects the excitability of GABAergic interneurons and synaptic transmission between primary nociceptive afferent and GABAergic interneurons. We found that a selective ${\mu}$-opioid agonist, [$D-Ala^2$, $NMe-Phe^4$, Gly-ol]-enkephanlin (DAMGO), induced an outward current mediated by $K^+$ channels in GABAergic interneurons. In addition, DAMGO reduced the amplitude of evoked excitatory postsynaptic currents (EPSCs) of GABAergic interneurons which receive monosynaptic inputs from primary nociceptive C fibers. Taken together, we found that DAMGO reduced the excitability of GABAergic interneurons and synaptic transmission between primary nociceptive C fibers and GABAergic interneurons. These results suggest one possibility that suppression of GABAergic interneurons by DMAGO may reduce the inhibition on secondary GABAergic interneurons, which increase the inhibition of the secondary GABAergic interneurons to excitatory neurons in the spinal dorsal horn. In this circumstance, the sum of excitation of the entire spinal network will control the pain transmission.

• Korean Journal of Pharmacognosy
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• v.51 no.3
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• pp.186-191
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• 2020

In this study, we evaluated the anti-nociceptive activities of Sorbus alnifolia. To investigate the anti-nociceptive properties of the methanolic extract of Sorbus alnifolia (MSA), we conducted several tests using various experimental mouse pain models. Herein, MSA significantly delayed the latency time and writhing motion in the hotplate test and acetic acid test, respectively. These result indicated that MSA has an ability to manage both peripheral and central nociception. We could further confirm the analgesic effects of MSA by performing formalin test. In combination test using naloxone, a non-selective opioid receptor antagonist, analgesic activity of MSA was partly antagonized by naloxone, but not completely, indicating that the MSA acts as a partial opioid receptor agonist. Out results suggest that the S. alnifolia may be possibly used as valuable anti-nociceptive agent.

• Journal of The Korean Dental Society of Anesthesiology
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• v.13 no.4
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• pp.167-178
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• 2013

Oxycodone is a semi-synthetic opioid synthesized from poppy-derived thebaine. It is a narcotic analgesic generally indicated for relief of moderate to severe pain. Although developed in an attempt to improve on the existing opioids, the adverse effects of oxycodone are those that are typically found in opioids. In recent years, the use of the opioid oxycodone has increased markedly and replacing morphine as the first line choice of opioid in several countries. There are formulations for oral immediate, oral extended release and intravenous use. In 2013, intravenous oxycodone was approved for marketing by Ministry of Food and Drug Safety (MFDS), with the indication of postoperative intravenous patient-controlled analgesia (IV PAC). Simulation study of oxycodone demonstrated that minimum effective analgesic concentration (MEAC) of oxycodone was most quickly reached with higher loading dose and IV PCA with background infusion, which may reduce the necessity of rescue analgesics during immediate postoperative period. Previous studies for postoperative pain management with intravenous oxycodone are limited in sample size, mostly less than 100 patients, which may not be large enough to assess safety of intravenous oxycodone. The effectiveness and tolerability of IV PCA with oxycodone should, therefore, be evaluated in large scale clinical trials in Korean populations.

• Korean Journal of Pharmacognosy
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• v.21 no.1
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• pp.103-109
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• 1990

The antagonism against clonidine-induced analgesia by ginseng saponin (GS) and the inhibitory effect of GS on the development of clonidine-induced tolerance were evaluated in mice. GS, when administered systemically, intracerebrally and intrathecally, antagonized significantly the analgesic effect of clonidine. GS, when injected intraperitoneally not only inhibited the development of clonidine-induced analgesic tolerance, but also enhanced the analgesic effect of clonidine on the 2nd and 5th day. Naloxone did not antagonize the analgesic effect of clonidine and had no influence on the deveolpment of tolerance of both acute and delayed types. These results indicate that the antagonism against clonidine-induced analgesia and the inhibition of the deveolpment of clonidine-induced tolerance by GS are not mediated by the opioid mechanism.

• Archives of Pharmacal Research
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• v.23 no.4
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• pp.391-395
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• 2000

To establish the usefulness of oxytocin (OT) as an analgesic for women in delivery, the pharmacokinetic parameters and blood-brain barrier (BBB) permeability of [$^3H$] OT were obtained using an intravenous injection technique or the internal carotid artery perfusion/capillary depletion (ICAP/CDM) method. Brain uptake of OT was similar to that of sucrose, plasma space marker, indicating that OT has a poor BBB permeability. Moreover, the analgesic effects of OT injected through the jugular vein on nociception were evaluated by the tail-flick method. The antinociceptive effects of OT injected at a dose of 0.2 ${m}g/kg$or 2 ${m}g/kg$ were dose-dependent. In addition, the analgesic effects of OT on the CNS were unaffected by naloxone, a m-receptor antagonist. In a similar manner to the opioid system, OT may play a modulatory role in antinociception.