• The Korean Journal of Physiology and Pharmacology
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• v.7 no.5
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• pp.251-254
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• 2003

The present study was designed to examine whether the co-application of morphine with $Ca^{2+}$ channel antagonist $(Mn^{2+},\;verapamil)$, N-methyl-D-aspartate (NMDA) receptor antagonist (2-amino-5-phosphonopentanoic acid$[AP_5]$, $Mg^{2+}$) or protein kinase C inhibitor (H-7) causes the potentiation of morphine-induced antinociceptive action by using an in vivo electrophysiological technique. A single iontophoretic application of morphine or an antagonist alone induced weak inhibition of wide dynamic range (WDR) cell responses to iontophoretically applied NMDA and C-fiber stimulation. Although there was a little difference in the potentiating effects, the antinociceptive action of morphine was potentiated when morphine was iontophoretically applied together with $Mn^{2+}$, verapamil, $AP_5$, $Mg^{2+}$ or H-7. However, the potentiating action between morphine and each antagonist was not apparent, when the antinociceptive action evoked by morphine or the antagonist alone was too strong. These results suggest that the potentiating effect can be caused by the interaction between morphine and each antagonist in the spinal dorsal horn.

• Archives of Pharmacal Research
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• v.25 no.2
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• pp.202-207
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• 2002

This study was performed to investigate the effect of tetrahydroisoxazolopyridine (THIP), a $GABA_A$ agonist, on the morphine-induced hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity in mice. A single administration of morphine induced hyperactivity in mice. However, the morphine-induced hyperactivity was inhibited dose-dependently by the administration of THIP (0.2, 0.4 and 0.8 mg/kg, i.p.). In contrast, daily administration of morphine resulted in a reverse tolerance to the hyperactivity caused by morphine (10 mg/kg ,s.c.). THIP inhibited the development of reverse tolerance in the mice that had received the repeated same morphine (10 mg/kg s.c.) doses. The postsynaptic dopamine receptor supersensitivity, which was evidenced by the enhanced ambulatory activity its after the administration of apomorphine (2 mg/kg s.c.), also developed in the reverse tolerant mice. THIP also inhibited the development of the postsynaptic dopamine receptor supersensitivity indulged by the chronic morphine administration. These results suggest that the hyperactivity, reverse toterance and postsynaptic dopamine receptor supersensitivity induced by morphine can be inhibited activating the $GABA_A$ receptors.

• The Korean Journal of Pharmacology
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• v.18 no.2
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• pp.33-44
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• 1982

The binding in vitro of an opiate agonist, $(^3H)-morphine$, was studied using rat brain slices which were incubated in the modified Krebs-Henseleit bicarbonate buffer solution containing various concentrations of electrolytes with or without morphine, naloxone or morphine+naloxone at $4^{\circ}C$ for 24 hours. The binding of $(^3H)-morphine$ may be seperated into two component; one a saturable binding and the other nonsaturable. The saturable binding may be calculated from the differences in binding observed in the absence and presence of high concentration of morphine. The maximal saturable binding and $K_D$ value in the naive preparations were $0.32{\pm}0.02\;pmole/mg$ protein and $0.75{\pm}0.07\;nM$ respectively. The saturable binding of $(^3H)-morphine$ was significantly increased by low temperature-treatment, while $K_D$ value was not changed. Morphine in the incubation media significantly increased the saturable binding of $(^3H)-morphine$ and $K_D$ value. Naloxone also increased the maximal saturable binding of $(^3H)-morphine$ and $K_D$ value of the drug. Decrease of $K^+\;and\;Mg^{++}$, and addition of $Mn^{++}$ in the incubation media significantly increased the saturable binding of $(^3H)-morphine$, but decrease of $Na^+$and increase of $Ca^{++}$ in the incubation media did not influence the binding. The increment of the saturable binding of $(^3H)-morphine$ by nonlabeled morphine in the incubation media was notaffected by decrease of $Na^+,\;K^+\;or\;Mg^{++}$, or addition of $Mn^{++}$ into the incubation media, but was inhibited by increase of $Ca^{++}$ in the incubation media, while the increment of the saturable binding of $(^3H)-morphine$ was net observed by decrease of $Na^+,\;K^+\;or\;Mg^{++}$, or increase of $Ca^{++}$ in the incubation media. The above results indicate that change of opiate binding sites in quality, i.e. affinity, and quantity, i.e. number of binding sites, may occur by low temperature-treatment in the absence and presence of morphine or naloxone and that electrolytes play role of the changes of opiate binding sites.

• Journal of Ginseng Research
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• v.11 no.2
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• pp.123-129
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• 1987

Antagonisms of the analgesic effect of morphine in mice by ginsenoside Rbl, Rb2, Rgl and Re were investigated in these experiments. These ginsenosides antagonized the analgesic effect induced by morphine in mice and the administration of 2,4-dihy-droxyphenylalanine or 5-hydroxytryptophan reduced the antagonisms of morphine analgesia by the ginsenosides. Possible mechanisms involved in the antagonistic actions of the ginsenosides on morphine analgesia were described.

• Proceedings of the PSK Conference
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• 2003.10a
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• pp.112-112
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• 2003

Morphine is a potent analgesic and addictive substance. Morphine produces neurotoxicity such as rewarding effect, analgesic tolerance and physical dependence. It has been restricted to the use of morphine in patients because of these problems. The present study was investigated the effect of berberine on the neurotoxicity of morphine. Repeated administration of morphine produced conditioned place prefernece (CPP) and behavioral sensitization in mice. (omitted)

• The Korean Journal of Pain
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• v.10 no.1
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• pp.28-33
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• 1997

Background : Analgesic effect of intra-articular morphine or ketoronac treatment alone, or a combination of both drugs, on postoperative pain were evaluated in 40 healthy male patients undergoing arthroscopic knee surgery. Method : Upon completion of surgery under spinal anesthesia, each patients knee joint was injected with 30 ml of 0.25% bupivacaine. Then, via parenteral or intra-articular route, one study group received morphine and other group received ketorolac. Results : Groups who received either intra-articular ketorolac, or morphine, experienced decreased postoperative pain reducing need for additional analgesics. The combination treatment of intra-articular morphine and ketorolac did not improved results. Conclusions : Singular use of either intra-articular morphine, or ketorolac, improves postoperative analgesia in patients undergoing arthroscopic sugery: Combination of these drugs offered no further advantage over its single prescription.

• Biomolecules & Therapeutics
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• v.30 no.4
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• pp.328-333
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• 2022

Repeated morphine administration induces tolerance to its analgesic effects. A previous study reported that repeated morphine treatment activates transient receptor potential vanilloid type 1 (TRPV1) expression in the sciatic nerve, dorsal root ganglion, and spinal cord, contributing to morphine tolerance. In the present study, we analyzed TRPV1 expression and binding sites in supraspinal pain pathways in morphine-tolerant mice. The TRPV1 mRNA levels and binding sites were remarkably increased in the cortex and thalamus of these animals. Our data provide additional insights into the effects of morphine on TRPV1 in the brain and suggest that changes in the expression of, and binding to TRPV1 in the brain are involved in morphine tolerance.

• The Korean Journal of Pain
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• v.13 no.2
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• pp.218-223
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• 2000

Background: This study was conducted to evaluate the efficacy of a parenteral nonsteroidal anti-inflammatory agent for management of post-surgical pain and its effect on hospital stay and long-term surgical outcome. Methods: Total of 40 patients undergoing lumbar discectomy were randomly assigned to two groups, receiving either 1) 30 mg intravenous ketorolac upon surgical closure, every 6 hours for 36 hours, and morphine IV PCA (intravenous patient controlled analgesia), or 2) only morphine PCA. A blinded investigator recorded; the visual analog pain scores, total postoperative narcotic consumption, complications by morphine PCA, length of hospitalization (from surgery to discharge), and long-term outcome at 6 weeks. Results: The patients who received IV ketorolac and morphine PCA reported significantly lower visual analog pain scores than patients receiving only morphine PCA. Cumulative morphine doses were significantly lower in the ketorolac group (P<0.001). There was no significant difference between groups in the frequency of side effects related to morphine PCA. Mean length of hospitalization was longer for patients receiving only morphine PCA, but there was no statistical significance. Six weeks after surgery, four (20.0%) patients who received only morphine PCA suffered persistent back pain. In contrary, all those patients who received ketorolac were free of back pain at follow-up (P<0.05). Conclusions: These results suggest that intermittent IV bolus ketorolac, when used with opioid IV PCA is more effective than opioid IV PCA alone for postoperative pain following lumbar disc surgery. However, this strategy did not contribute to early discharge from hospital after lumbar disc surgery. The effect to long-term surgical outcome was not conclusive.

• The Korean Journal of Pain
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• v.11 no.1
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• pp.1-6
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• 1998

Background: The role of nitric oxide(NO) in analgesia from opioids is controversial. On the one hand, IV morphine analgesia is enhanced by IV injection of NO synthase inhibitors. On the other hand, IV morphine results in increased release of NO in the spinal cord. There have been no behavioral studies examining the interaction between IV morphine and intrathecal injection of drugs which affect NO synthesis. Method: Rats were prepared with chronic lumbar intrathecal catheters and were tested withdrawal latency on the hot plate after 3~5 days of surgery. Antinociception was determinined in response to a heat stimulus to the hind paw before and after IV injection of morphine, 2.5 mg/kg. Twenty minutes after morphine injection, rats received intrathecal injection of saline or the NO synthase inhibitors, L-NMMA or TRIM, the NO scavenger, PTIO, or the NO synthase substrate, L-Arginine. Intrathecal injections, separated by 15 min, were made in each rats and measurements were obtained every 5 min. Result: Mophine produced a 60~70% maximal antinociceptive response to a heat stimulus in all animals for 60 min in control experiments. Intrathecal injection of idazoxane decreased antinociception of IV morphine. The NO synthase inhibitors and the NO scavenger produced dose-dependent decreases in antinociceptive effect of morphine, whereas saline as a control group and L-Arginine as the NO substrate had no effect on antinociception of morphine. Conclusion: The present study supports the evidences that systemic morphine increase the nitrite in cerebrospinal fluid and dorsal horn. These data suggest that the synthesis of NO in the spinal cord may be important to the analgesic effect of IV morphine and increased NO in spinal cord has different action from the supraspinal NO.

• The Korean Journal of Pain
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• v.7 no.2
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• pp.188-192
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• 1994

Recently, epidural morphine has been administrated to decrease patients' systemic stress responses such as: suffers, endocrine responses and impairment of pulmonary function, etc. Epidural morphine provided excellent analgesic effect, but incomplete sensory blockade as compared to epidural local anesthetics, which has sympathetic blockade effect and tachyphylaxis. Therefore, the authors surmised that low dose bupivacaine on low dose epidural morphine improved postoperative pain with greater sensory analgesia than epidural morphine alone. The effect of low dose bupivacaine on epidural morphine analgesia for postoperative pain was evaluated in seventy patients. They were physical status I-III by ASA classification. Patients were randomly divided into 2 groups and they were administrated morphine 2.5 mg only (group I), morphine 2.5 mg plus 0.125% bupivacaine (group II) through epidural catheter 1 hour before the end of the operation. During postoperative second days, their analgesic effects were evaluated by visual analogue scale (0-10). Side effects were also evaluated. The results were as follows, 1) On the day of the operation, VAS score showed significant differences between two groups (morphine group $3.20{\pm}0.16$, morphine plus bupivacaine group $2.77{\pm}0.08$; p < 0.05). 2) On the postoperative and second day, there were no statistical differences between the groups according to VAS score. 3) The incidence of pruritus, nausea, and vomiting were no differences in both groups. 4) None of the patients showed objective sedation or a low respiratory rate (< 10 bpm). We concluded that epidural administration of low dose bupivacaine on the epidural morphine analgesia was an effective method to decrease postoperative pain with little change in frequencies of side effects compared to epidural morphine alone.