• The Korean Journal of Pain
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• v.18 no.2
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• pp.124-132
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• 2005

Background: This study was performed to evaluate the dose-related effects of naloxone on morphine analgesia in the rat formalin test, and observe the correlation of pain behavior and spinal c-fos expression induced by a formalin injection. Methods: Fifty rats were divided into five groups; control, morphine (morphine pre-treated, intra-peritoneal injection of 0.1 mg of morphine 5 min prior to formalin injection), and three naloxone groups, which were divided according to the administered dose-ratio of naloxone to morphine 20 : 1 ($5{\mu}g$), 10 : 1 ($10{\mu}g$), and 1 : 1 ($100{\mu}g$) representing the low-, medium-, and high-dose naloxone groups, respectively, were injected intra-peritoneally 16 min after a formalin. A fifty ul of 5% formalin was injected into the right hind paw. All rats were observed for their pain behavior according to the number of flinches during phases 1 (2-3, 5-6 min) and 2 (1 min per every 5 min from 10 to 61 min). The spinal c-fos expression was quantitatively analyzed at 1 and 2 hours after the formalin injection using a real-time PCR. Results: The morphine pre-treated (morphine and three naloxone) groups during phase 1, and the morphine, low- and medium-dose naloxone groups during phase 2, showed significantly less flinches compared to those of the control (P < 0.05). In the three naloxone groups, the numbers of flinches were transiently reduced following the naloxone injection in the low- and medium-dose groups compared to those of the morphine group (P < 0.05). The duration of the reduced flinches was longer in the medium-dose group (P < 0.05). The high-dose group revealed immediate increases in flinches immediately after the naloxone injection compared to those of the morphine, low- and medium-dose groups (P < 0.05 for each). The spinal c-fos expression showed no significant patterns between the experimental groups. Conclusions: Our data suggest that relatively low-dose naloxone (1/20 to 1/10 dose-ratio of morphine) transiently potentiates morphine analgesia; whereas, high-dose (equal dose-ratio of morphine) reverses the analgesia, and the spinal c-fos expression does not always correlate with pain behavior in the rat formalin test.

• The Korean Journal of Pain
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• v.3 no.2
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• pp.125-130
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• 1990

One hundred patients requiring appedectomy were studied to determine the minimal effective dose of intrathecal morphine for postoperative analgesia. In double-blind fashion, groups of 20 patients received either 0.02 mg (group I), 0.04 mg (group II), 0.06 mg (group III), 0.08 mg (group IV), or 0.10 mg (group V) intrathecally with 10% dextrose in water 2 ml. Group II to group V patients reported significantly less postoperative pain than group I patients as assessed by the Prince Henry pain scale and required significantly fewer analgesic interventions for 24 hours. The incidences of vomiting and pruritus were considerably high in all groups, but none of them required any treatment. The incidence of urinary catheterization due to urinary retention in group II to V was twice that of group I. No clinically evident respiratory depression occurred in any of the subjects. In conclusion, intrathecal morphine administration of 0.04 mg proved effective in reducing postoperative analgesic requirements and in eliminating postoperative pain following appendectomy and was not associated with significant side effects. It is very likely that such low dose intrathecal morphine would also work in other operations.

• Journal of Hospice and Palliative Care
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• v.5 no.1
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• pp.24-30
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• 2002

Background : Pain is one of the most feared consequences of cancer. $65{\sim}85%$ of cancer patients experienced severe pain, and sometimes high dose morphine is used to these patients. But many doctors still have 'opioid-phobia' and hesitate to use high dose morphine. We investigated the morphine therapy in terminal cancer patients during the last 1 week to death, and found any differences according to the morphine dosage. Methods : 93 patients admitted to National Health Insurance Corporation Ilsan Hospital, department of family medicine for hospice care between September 2000 and the end of October 2001 and lived more than 1 week entered in the study. We investigated the demographic data, laboratory tests and sufficient dosage of morphine for pain control. According to the calculated dosage by OME(oral morphine equivalent), patients were divided into low dosage group (${\leq}150mg/day$) and high dosage group (>150 mg/day). The chi-squared test were used to evaluate the influence of age, gender, tumor sites, metastasis and adverse effects of morphine. Results : Mean age was $65.0{\pm}13.1year$ in low dosage group and $59.9{\pm}11.6year$ in high dosage group. 32 men (50.0%) and 32 women (50.0%) were included in low dosage group and 15 men (51.7%) and 14 women (48.3%) in high dosage group. Stomach was the most frequent tumor site and lung was the next. Metastasis were found 58 (90.6%) in low dosage group and 28 (96.6%) in high dosage group. In other palliative radiotherapy and adverse effects, there were no differences in both group. Conclusion : During the last 1 week to death in cancer patients, there were no difference according to the morphine dosage. So we don't have to have 'opioid-phobia' in treating the terminal cancer patients.

• The Korean Journal of Pain
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• v.35 no.1
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• pp.66-77
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• 2022

Background: Thrombospondin-4 (TSP4) upregulates in the spinal cord following peripheral nerve injury and contributes to the development of neuropathic pain (NP). We investigated the effects of cyanocobalamin alone or in combination with morphine on pain and the relationship between these effects and spinal TSP4 expression in neuropathic rats. Methods: NP was induced by chronic constriction injury (CCI) of the sciatic nerve. Cyanocobalamin (5 and 10 mg/kg/day) was administered 15 days before CCI and then for 4 and 14 postoperative days. Morphine (2.5 and 5 mg/kg/day) was administered only post-CCI. Combination treatment included cyanocobalamin and morphine, 10 and 5 mg/kg/day, respectively. All drugs were administered intraperitoneally. Nociceptive thresholds were detected by esthesiometer, analgesia meter, and plantar test, and TSP4 expression was assessed by western blotting and fluorescence immunohistochemistry. Results: CCI decreased nociceptive thresholds in all tests and induced TSP4 expression on the 4th postoperative day. The decrease in nociceptive thresholds persisted except for the plantar test, and the increased TSP4 expression reversed on the 14th postoperative day. Cyanocobalamin and low-dose morphine alone did not produce any antinociceptive effects. High-dose morphine improved the decreased nociceptive thresholds in the esthesiometer when administered alone but combined with cyanocobalamin in all tests. Cyanocobalamin and morphine significantly induced TSP4 expression when administered alone in both doses for 4 or 14 days. However, this increase was less when the two drugs are combined. Conclusions: The combination of cyanocobalamin and morphine is more effective in antinociception and partially decreased the induced TSP4 expression compared to the use of either drug alone.

• Journal of Hospice and Palliative Care
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• v.11 no.3
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• pp.136-139
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• 2008

Purpose: Epidural morphine infusion has been used to control pain in cancer patients whose cancer pain can not be controlled high dose intravenous morphine injection. To study the effectiveness and side effects of epidural morphine for the treatment of cancer pain in terminal patients at Hospice Ward, we evaluated the change in morphine equivalent daily dose for effectiveness and complications of epidural morphine infusion. Methods: We retrospectively analyzed 24 terminal cancer patients who were treated with continuous epidural morphine between 2001 and 2004 at Hospice Ward of St. Vincent's Hospital. Results: The median of baseline morphine equivalent daily dose was 615 mg, whereas the median dose of initial epidural morphine was 16 mg. The median of morphine daily equivalent daily dose dropped from 615 mg to 274 mg in one week after epidural morphine infusion therapy (P-value=0.000). The median survival from the time of the first catheter insertion was 35 days. In 6 patients, the catheter was removed due to complications, however the catheter was reinserted in 3 patients. Conclusion: Cancer pain management by epidural morphine infusion is very effective method with low rate of severe complication.

• The Korean Journal of Pain
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• v.19 no.1
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• pp.96-100
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• 2006

Pain control is very important in managing terminal cancer patients and there are several modalities to alleviate their pain. A high dosage of epidural morphine is effective to control terminal cancer pain. Furthermore, to decrease the amount of morphine, adding an alternative adjuvant like ketamine to the morphine regimen is considered helpful for controlling the pain of a terminal cancer patient. A 45 year old male patient with terminal lung cancer had neck pain that was caused by multiple bone metastases. Continuous epidural block was started with 2 mg/day of morphine and the dosage was gradually increased to 90 mg/day in 86 days. 30 mg/day of ketamine was then added to it. Overall, the morphine and ketamine dosages were increased to 564 mg/day and 140 mg/day, respectively, in 11 months until the patient expired. In this case, the high dosage of epidural morphine, 580 mg/day, was administered to control cancer pain without any severe adverse effects.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.294-294
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• 1994

To investigate analgesic mechanism of capsaicin and its analogues (capsaicinoids), release of adenosine was measured by high performance liquid chromatography from dorsal spinal cord synaptosomes, Exposure of synaptosomes to K$\^$+/ and morphine produced a dose dependent release of adenosine in the presence of Ca$\^$++/. Capsaicin (0.1, 1, 10 M), and its analogues 6-paradol (1, 10 M), NE-19550 (1, 10, 100 M), DMNE (1, 10, 100 M) and KR 25018 (0.1, 1, 10 M) produced a dose dependent release of adenosine in the presence of Ca$\^$++/. Nifedipine, L-type voltage sensitive calcium channel blocker, inhibited K$\^$+/ (6, 12 mM)- and morphine (10 M)-evoked release of adenosine completely, but inhibited capsaicin, and capsaicinoids-evoked release of adenosine partially. Capsazepine, a novel capsaicin select ive antagonist, blocked only capsaicin and capsaicinoids induced release of adenosine. Therefore, the adenosine release by capsaicin and capsaicinoids having antinociceptive effects involve activation of capsaicin specific receptor and capsaicin sensitive Ca$\^$++/ channel.

• The Korean Journal of Pain
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• v.10 no.2
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• pp.170-178
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• 1997

Background: The analgesic efficacy and safety of propacetamol, an injectable prodrug of acetoaminophen, in combination with intravenous morphine PCA were studied in 40 patients after gynecological surgery requiring lower abdominal incision. Methods: Using a double-blind, randomized, parallel-group design, the effects of four(every 6 hr) intravenous injections of 2 g propacetamol(=1 g acetoaminophen) were compared with four injections of placebo(PL) immediately after surgery. Efficacy of cumulative dose of morphine and number of boluses requested was assessed over 24 hours by automated recording on the PCA device. It was assessed on pain scores rated on a ten-point verbal scale along with vital signs, $K^+$, glucose, BUN, creatinine, PT and PTT were measured along with stress hormones(epinephrine, norepinephrine and cortisol). Results: There were no differences in demographic data between two groups. Propacetamol group demonstrated approximately 21% morphine sparing effect compared to placebo group($33.1{\pm}10.4$ mg vs $41.4{\pm}8.0$ mg). No significant differences noted in $K^+$, glucose, BUN, Creatinine, PT and PTT levels. There were significant increases in norepinephrine and cortisol in placebo group postoperatively, compared to preoperative values. At the same time, propacetamol group also showed significant changes in these hormones. Both group revealed high degree of patient satisfaction. Conclusion: Propacetamol showed significant morphine sparing effect to some degree. Side effects were much less in propacetamol group with subsequently high patient satisfaction. The secretion of stress hormone were not blocked by postoperative propacetamol injections. Authors concluded that propacetamol should be considered as an excellent adjuvant analgesics in postoperative pain control in opioid patient controlled analgesia.

• The Korean Journal of Pain
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• v.6 no.2
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• pp.213-219
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• 1993

The use of buprenorphine by epidural route in the prevention of postoperative pain has been controversial. High lipid solubility of buprenorphine caused the same parenteral/epidural analgesic dose ratio, and the analgesic effect of epidural buprenorphine possibly due to systemic absorption, which revealed no advantages of epidural administration against parenteral injection. On the contrary, epidural buprenorphine had longer duration of action and fewer side effects than parenteral buprenorphine, which advocated the epidural use of buprenorphine. We studied the efficacy of epidural buprenorphine by comparing epidural buprenorphine with epidural morphine in terms of latency and the duration of analgesic action, and the incidence of side effects. 0.15mg and 0.3mg of epidural buprenorphine had shorter latency than 2mg of morphine. 0.3 mg of buprenorphine had longer duration of action than 4 mg of morphine. The incidence of nausea and vomiting were slightely higher in buprenorphine group than in morphine group. Voiding difficulty and pruritus were little in buprenorphine group, while the incidence of somnolence was markedly higher in buprenorphine group. Form our results we conclude that epidural buprenorphine may be useful in the treatment of postoperative pain, and but recognize both advantages and disadvantages as compared epidural morphine.

• YAKHAK HOEJI
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• v.43 no.1
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• pp.55-60
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• 1999

To investigate analgesic mechanism of capsaicin and its analogues (capaicinoids) adenosine release was measured by high performance liquid chromatography from rat spinal cord synaptosomes. Exposure of synaptosomes to $K^+$ and morphine produced a dose dependent release of adenosine in the presence of $Ca^{++}$. Capsaicin (0.1, 1, $10{\;}{\mu}M$), and its analogues: NE-19550 (1, 10, $100{\;}{\mu}M$), DMNE (1, 10, $100{\;}{\mu}M$) and KR 25018 (0.1, 1, $10{\;}{\mu}M$) produced a concentration dependent release of adenosine in the presence of $Ca^{++}$. Nifedifine, L-type voltage sensitive calcium channel blocker, inhibited $K^+$ (6, 12 mM)-and morphine ($10{\;}{\mu}M$)-evoked release of adenosine partially. Capsazepine, a novel capsaicin selective antagonist, blocked only capsaicin and capsaicinoids induced release of adenoside. Therefore, it is suggested that the adenosine release by capsaicin and capsaicinoids having antinociceptive effects involves actvation of capsaicin specific receptor and capsaicin sensitive $Ca^{++}$. channel.