• 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.

• 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.

• Toxicological Research
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• v.19 no.4
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• pp.311-314
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• 2003

This study was performed to investigate the effects of glycine on the development of tolerance to and physical dependence on morphine. Repeated administration of morphine (10 mg/kg) developed tolerance and physical dependence. Glycine (100, 200 and 400 mg/kg) was administered intraperitoneally (i.p.) to mice for 7 days prior to the morphine injection. Analgesic effects were estimated by the tail flick methods. The inhibitory degree of the development of morphine-induced analgsic tolerance by i.p. administration of glycine was evidenced by the increase in analgesic response to morphine. Glycine inhibited the development of tolerance to morphine. In addition, we separately measured jumping response as the naloxone-precipitated withdrawal sign in mice that had received the same morphine. Glycine reduced the number of jumping behaviors in morphine dependent mice. These results suggest that glycine might be useful the prevention or treatment of morphine tolerance and physical dependence.

• Toxicological Research
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• v.11 no.1
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• pp.63-68
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• 1995

N-methyl-D-aspartate(NMDA) receptor has been well known as an important mediator of several forms of neural and behavioral plasticity. But different results were reported about the effect of MK-801 or dextromethorphan on opioid dependence. The present studies examined whether NMDA receptor antagonists can alter the opioid dependence and tolerance in rodents. Naloxone precipitated withdrawal symptoms and changes of locomotor activities were observed in MK-801 or dextromethorphan pretreated morphine-dependent rats. Tail-flick assay was used for morphine analgesia and tolerance was found after 4 day's consecutive injections (10 mg/kg, s.c., twice/day) of morphine in mice. Locomotor activity was increased and the withdrawal symptoms were decreased by the pretreatment of MK-801 in morphine-dependent rats. But 0.3 mg/kg i.p. of MK-801 intensified the body weight loss and produced severe ataxia and rotation although some withdrawal signs were attenuated. Morphine induced analgesic tolerance was inhibited by the pretreatment of MK-801 and dextromethorphan. Dextromethorphan was more potent than MK-801 in inhibiting the development of the analgesic tolerance in mice. These results suggest that NMDA system may be involved in opioid withdrawal and analgesic tolerance but appropriate caution should be requested when MK-801 is used in combination with opioid because of untoward neurologic signs.

• Korean Journal of Pharmacognosy
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• v.16 no.1
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• pp.31-35
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• 1985

Intraperitoneal administration of ginseng butanol fraction(GBF) to chronic morphinization in male Sprague-Dawley rats inhibited the development of tolerance to the analgesic effect and hyperthermic action of morphine. Rats were rendered tolerant to morphine by subcutaneous multiple morphine injections for a period of 8 days. The development of tolerance was evidenced by the decreased analgesic response to morphine and inhibition of tolerance by the greater analgesic response. Concomitant administration of morphine with GBF blocked the tolerance to the hyperthermic effect of morphine as evidenced by elevation of body temperature by morphine. Dopamine receptor sensitivity was enhanced in morphine tolerant rats as measured by apomorphine induced in spontaneous motor activity. GBF administration also blocked dopamine receptor supersensitivity induced by chronic morphinization.

• Journal of Ginseng Research
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• v.16 no.2
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• pp.93-98
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• 1992

This study examined the Influence of ginseng total saponins (GTS) on the analgestic action and tolerance development of pentazocine in mice. Pentazocine prolonged the latency to response in the tail flick rather than in the tail pinch test. The analgesic effect of pentaEocine was antagonized by naloxone and completely eliminated by pretreatment u·ith f-chlorophenylalanine (PCPA). GTS provented the pentasocine-incuced analgesia ann inhibited the development of tolerance to pentazocine. The antagonistic effect of GTS on the pentazocine-induced analgesia was abolished by 5-HTP, but not by L-DOPA. These results suggest that GTS inhibits the analgesic action of pentazocine by the interaction with serotonergic neuron.

• Natural Product Sciences
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• v.13 no.1
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• pp.46-53
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• 2007

The effects of the alcoholic extract of Bacopa monniera (BMA) on morphine-induced pharmacological activities were studied in mice. Oral administration of the extract (40 mg/kg) significantly inhibited morphine-induced analgesic tolerance, withdrawal symptoms, hyperactivity, reverse tolerance, Dopamine receptor supersensitivity and apo-morphine-induced climbing behaviour in mice. The results of this study showed that, alcoholic extract of Bacopa monniera (BMA) exerted inhibitory effect against morphine-induced pharmacological effects, suggesting that the extract could be useful in the treatment of morphine toxicity.

• Journal of Ginseng Research
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• v.13 no.1
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• pp.8-13
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• 1989

The effects of orally administered ginseng leaf saponins(GLS) on the analgesic action of morphine, the development of morphine induced tolerance and physical dependence, and the hepatic flutathione contents in mice were investigated. GLS antagonized the analgesic action of morphine and inhibited the development of morphine induced tolerance and physical dependence. It also inhibited the decrease in hepatic glutathione level induced by multiple injections of morphine.

• 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.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.47 no.1
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• pp.15-19
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• 2021

Objectives: The aim of this study was to evaluate correlations between anxiety and preoperative pressure pain assessments and postoperative pain and analgesic requirements in impacted lower third molar tooth surgery. Materials and Methods: This prospective study enrolled 60 patients who underwent impacted lower third molar surgery. The preoperative State-Trait Anxiety Inventory-I (STAI-I), pressure pain threshold, and pressure pain tolerance scores were measured. At 2, 4, 6, 12, and 24 hours, and at 6 days following surgery, the patients scored their pain on the visual analogue scale and recorded their analgesic drug usage. The data were evaluated, and the results were statistically analyzed. Results: Of the 60 patients, 38 were female. Mean age was 24.62±7.42 years. The study found no relationship between preoperative pressure pain assessments and postoperative pain (P>0.05). There was also no relationship observed between preoperative STAI-I scores and postoperative pain (P>0.05). However, there was a positive correlation between operation time and total medication taken (P<0.05). Conclusion: Preoperative pressure pain threshold, pressure pain tolerance, and anxiety level had no significant effects on postoperative pain and analgesic requirements in impacted lower third molar surgery.