• The Korean Journal of Pain
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• 제26권1호
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• pp.32-38
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• 2013

Background: Intrathecal opioid administration has been used widely in patients suffering from severe cancer pain that is not managed with conventional modalities. However, the potential serious neurological complications from the procedure and the side effects of intrathecal opioids have made many clinicians reluctant to employ continuous intrathecal analgesia as a first-line therapeutic option despite its dramatic effect on intractable pain. We retrospectively investigated the efficacy, side effects, and complications of intrathecal morphine administration through intrathecal catheters connected to a subcutaneous injection port (ICSP) in 22 Korean terminal cancer patients with successful intrathecal morphine trials. Methods: Patient demographic data, the duration of intrathecal opioid administration, preoperative numerical pain rating scales (NRS) and doses of systemic opioids, side effects and complications related to intrathecal opioids and the procedure, and the numerical pain rating scales and doses of intrathecal and systemic opioids on the $1^{st}$, $3^{rd}$, $7^{th}$ and $30^{th}$ postoperative days were determined from medical records. Results: Intrathecal morphine administration for $46.0{\pm}61.3$ days significantly reduced NRS from baseline on all the postoperative days. A significant increase in intrathecal opioids with a nonsignificant decrease in systemic opioids was observed on the $7^{th}$ and $30^{th}$ postoperative days compared to the $1^{st}$ postoperative day. The most common side effects of intrathecal opioids were nausea/vomiting (31.8%) and urinary retention (38.9%), which were managed with conservative therapies. Conclusions: Intrathecal morphine administration using ICSP provided immediate and beneficial effects on pain scores with tolerable side effects in terminal cancer patients.

• The Korean Journal of Pain
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• 제22권3호
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• pp.199-205
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• 2009

Background: A major ingredient of green tea is epigallocatechin-3-gallate (EGCG), and this is known to have many beneficial effects for cancer prevention and also on the cardiovascular system and neurodegenerative diseases through its anti-oxidant, anti-angiogenic, anti-inflammatory, lipid-lowering and neuroprotective properties. Its actions on nociception and the spinal nervous system have been examined in only a few studies, and in these studies EGCG showed an antinociceptive effect on inflammatory and neuropathic pain, and a neuroprotective effect in motor neuron disease. This study was performed to investigate the effect of EGCG on acute thermal pain and the development of morphine tolerance at the spinal level. Methods: The experimental subjects were male Sprague-Dawley rats and the Hot-Box test was employed. A single or double-lumen intrathecal catheter was implanted at the lumbar enlargement for drug administration. An osmotic pump was used to infuse morphine for 7 days for induction of morphine tolerance. EGCG was injected repeatedly for 7 days at twice a day through the intrathecal catheter. Results: Intrathecal EGCG increased the paw withdrawal latency (PWL) after repeated administration for 7 days at twice a day, but this did not happen with administering on single bolus injection of EGCG. In addition, the antinociceptive effect of intrathecal morphine was not affected by co-administration with EGCG. A continuous 7-day infusion of morphine caused a significant decrease of the PWL in the control group (M + S, morphine plus saline). In contrast, intrathecal EGCG injection over 7 days blocked the decrease of the PWL in the experiment group (M + E, morphine plus EGCG). Conclusions: Intrathecal ECGC produced a weak antinociceptive effect for acute thermal pain, but it did not change the morphine's analgesic effect. However, the development of antinociceptive tolerance to morphine was attenuated by administering intrathecal EGCG.

• The Korean Journal of Pain
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• 제11권1호
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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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• 제13권2호
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• pp.259-262
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• 2000

There are many difficulties in the management of terminal cancer pain. We often encounter difficulties when nerve blocks or epidural injection of drugs do not produce good results. Local anesthetics, opioids and adjunctives, were administered to two patients intrathecally. The results were very satisfactory. It has complications such as hypotension or infection due to intrathecal route. In the first case, the pancreatic cancer patient complicated with severe epigastic pain but unfortunately no management was effective in pain control. Intrathecal injection of bupivacaine and morphine mixture was successful even if syncope which was relieved by bed rest. In the second case, the patient complicated with lower abdominal pain due to ovarian cancer who very well controlled by epidural injection of morphine and clonidine mixture but morphine demand was greatly increased. Intrathecal injection of morphine and ketamine were tried. The patient had comportable analgesic effect. CSF leakage to subcutaneous occurred but resolved by change of the catheter position or retunnelling. There were no significant complications reported in two cases.

• The Korean Journal of Pain
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• 제18권2호
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• pp.99-106
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• 2005

Background: Cyclic guanosine monophosphate (cGMP) and opioid receptors are involved in the modulation of nociception. Although the opioid receptors agonists are active in pain, the effect of an phospodiesterase inhibitor (zaprinast) for increasing the level of cGMP has not been thoroughly investigated at the spinal level. This study examined the effects of intrathecal zaprinast and morphine in a nociceptive test and we also examined the nature of the pharmacological interaction after the coadministration of zaprinast with morphine. The role of the nitric oxide (NO)-cGMP-potassium channel pathway on the effect of zaprinast was further clarified. Methods: Catheters were inserted into the intrathecal space of male SD rats. For the induction of pain, $50{\mu}l$ of 5% formalin solution was applied to the hindpaw. Isobolographic analysis was used for the evaluation of the drug interaction between zaprinast and morphine. Furthermore, NO synthase inhibitor ($_L-NMMA$), guanylyl cyclase inhibitor (ODQ) or a potassium channel blocker (glibenclamide) were intrathecally administered to verify the involvement of the NO-cGMP- potassium channel pathway on the antinociception effect of zaprinast. Results: Both zaprinast and morphine produced an antinociceptive effect during phase 1 and phase 2 in the formalin test. Isobolographic analysis revealed a synergistic interaction after the intrathecal administration of the zaprinast-morphine mixture in both phases. Intrathecal $_L-NMMA$, ODQ and glibenclamide did not reverse the antinociception of zaprinast in either phase. Conclusions: These results suggest that zaprinast, morphine and the mixture of the two drugs are effective against acute pain and they facilitated pain state at the spinal level. Thus, the spinal combination of zaprinast with morphine may be useful for the management of pain. However, the NO-sensitive cGMP-potassium channel pathway did not contribute to the antinocieptive mechanism of zaprinast in the spinal cord.

• The Korean Journal of Pain
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• 제13권1호
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• pp.55-59
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• 2000

Background: Intrathecal injection of morphine is widely used in the management of postoperative pain because it provides long-lasting analgesia. Intramuscular caroverine and tiaprofenate are used to produce postoperative pain relief. This study was designed to evaluate the analgesic efficacy and quality of sleep achieved with intrathecal morphine and those of intramuscular caroverine and tiaprofenate in transurethral resection of the prostate (TURP). Methods: Forty patients undergoing elective TURP were randomly allocated into 2 groups as follows: Group M (n=20); 0.25 mg of morphine hydrochloride mixed in 7.5 mg of 0.5% hyperbaric bupivacaine was administered at the time of induction of spinal anesthesia. Group S (n=20); 7.5 mg of 0.5% hyperbaric bupivacaine was administered intrathecally and caroverine and tiaprofenate intramuscularly at every 8 hr and 12hr postoperatively for management of postoperative pain. We evaluated the analgesic efficacy with visual analog scale (VAS), quality of sleep, and side effects. Results: VAS at 6, 12 and 24 hours after operation were significantly less (p<0.01) in the group M than in the group S. Group M was superior to group S with respect to quality of sleep (p<0.01). In the group M, the incidence of nausea was 30% (6/20) and that of pruritus was 35% (7/20) and clinical respiratory depression did not occur. Conclusions: Intrathecal 0.25 mg morphine provides good postoperative analgesic effect. but intramuscular caroverine and tiaprofenate does not.

• The Korean Journal of Pain
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• 제3권2호
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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.

• The Korean Journal of Pain
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• 제22권1호
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• pp.74-77
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• 2009

Implantable intrathecal pump is one of the therapeutic options for intractable pain. A 24-year-old male with complex regional pain syndrome was suffering from right lower extremity pain. He had all modalities of treatment including spinal cord stimulator. However, his pain had been worse in the past 6 months. His visual analogue pain scale (VAS) was 8-10 and he could not sit or walk. Only opioid was thought to be effective. Then, intrathecal pump was considered. We estimated the minimal effective dose of spinal morphine before implantation. 0.3 mg of morphine was injected intrathecally as a starting dose. Dosage had been increased up to 0.8 mg in 10 days. His VAS score decreased from 8 to 5. He could sleep without pain and walk with crutch. Therefore, intrathecal pump was inserted. He could tolerate to pain. This case suggests that intrathecal morphine delivery can provide effective treatment for intractable non-malignant pain.

• The Korean Journal of Pain
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• 제25권2호
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• pp.126-129
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• 2012

Opioid analgesia is the primary pharmacologic intervention for managing pain. However, opioids can cause various adverse effects including pruritus, nausea, constipation, and sedation. Respiratory depression is the most fatal side effect. Therefore, cautious monitoring of respiratory status must be done after opioid administration. Here, we report a patient who suffered from respiratory depression with deep sedation and aspiration pneumonitis after intrathecal morphine administration.

• The Korean Journal of Pain
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• 제1권2호
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• pp.188-191
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• 1988

Recent studies have shown that narcotic drugs produce an intense prolonged analgesic action when injected into the subarachnoidal or extradural space of animals and man. In order to study the effects of intrathecal injection of morphine on postoperative pain relief and segmental block effect, we administered 0.25 mg of morphine sulfate (0.25 mg of morphine/1 ml normal saline) into lumbar subarachnoid space prior to brahial plexus block for upper extremity surgery group The results were as follows: 1) more than 20 hours analgesic effect at least 2) no segemental block effect in analgesia 3) some adverse effect (Nausea, Vomiting, Pruritus, Urinary retention).