• The Korean Journal of Pain
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• 제25권1호
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• pp.1-6
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• 2012

Background: Curcumin has been reported to have anti-inflammatory, antioxidant, antiviral, antifungal, antitumor, and antinociceptive activity when administered systemically. We investigated the analgesic efficacy of intrathecal curcumin in a rat model of inflammatory pain. Methods: Male Sprague Dawley rats were prepared for intrathecal catheterization. Pain was evoked by injection of formalin solution (5%, $50{\mu}l$) into the hind paw. Curcumin doses of 62.5, 125, 250, and $500{\mu}g$were delivered through an intrathecal catheter to examine the flinching responses. The $ED_{50}$ values (half-maximal effective dose) with 95% confidence intervals of curcumin for both phases of the formalin test were calculated from the dose-response lines fitted by least-squares linear regression on a log scale. Results: In rats with intrathecal administration of curcumin, the flinching responses were significantly decreased in both phases. The slope of the regression line was significantly different from zero only in phase 2, and the $ED_{50}$ value (95% confidence interval) of curcumin was $511.4{\mu}g$ (23.5-1126.5). There was no apparent abnormal behavior following the administration of curcumin. Conclusions: Intrathecal administration of curcumin decreased inflammatory pain in rats, and further investigation to elucidate the precise mechanism of spinal action of curcumin is warranted.

• The Korean Journal of Pain
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• 제30권2호
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• pp.98-103
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• 2017

Background: The root of Peucedanum japonicum Thunb., a perennial herb found in Japan, the Philippines, China, and Korea, is used as an analgesic. In a previous study, sec-O-glucosylhamaudol (SOG) showed an analgesic effect. This study was performed to examine the antinociceptive effect of intrathecal SOG in the formalin test. Methods: Male Sprague-Dawley rats were implanted with an intrathecal catheter. Rats were randomly treated with a vehicle and SOG ($10{\mu}g$, $30{\mu}g$, $60{\mu}g$, and $100{\mu}g$) before formalin injection. Five percent formalin was injected into the hind-paw, and a biphasic reaction followed, consisting of flinching and licking behaviors (phase 1, 0-10 min; phase 2, 10-60 min). Naloxone was injected 10 min before administration of SOG $100{\mu}g$ to evaluate the involvement of SOG with an opioid receptor. Dose-responsiveness and ED50 values were calculated. Results: Intrathecal SOG showed a significant reduction of the flinching responses at both phases in a dose-dependent manner. Significant effects were showed from the dose of $30{\mu}g$ and maximum effects were achieved at a dose of $100{\mu}g$ in both phases. The ED50 value (95% confidence intervals) of intrathecal SOG was 30.3 $(25.8-35.5){\mu}g$ during phase 1, and 48.0 (41.4-55.7) during phase 2. The antinociceptive effects of SOG ($100{\mu}g$) were significantly reverted at both phases of the formalin test by naloxone. Conclusions: These results demonstrate that intrathecal SOG has a very strong antinociceptive effect in the formalin test and it seems the effect is related to an opioid receptor.

• 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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• 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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• 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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• 제30권3호
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• pp.207-213
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• 2017

Background: Surgeon satisfaction and patient analgesia during the procedure of laparoscopic surgery are important issues. The aim of this work was to study if an intrathecal (IT) Bupivacaine combined with Magnesium sulfate may or may not provide good surgeon satisfaction in addition to improvement of intraoperative and postoperative analgesia. Methods: Sixty female patients were enrolled in this prospective, randomized, double-blind controlled clinical trial study. All patients were operated for gynecological laparoscopic surgery under spinal anesthesia. Patients were divided into two groups (Bupivacaine and Magnesium). Group Bupivacaine (30 patients) received intrathecal Bupivacaine 0.5% only (15 mg), while 30 patients in group Magnesium received intrathecal Bupivacaine (15 mg) in addition to intrathecal Magnesium sulfate (50 mg). The sensory block level, the intensity of motor block, the surgeon satisfaction, the intraoperative visual analog scale (VAS) for pain assessment, the postoperative VAS, and side effects were recorded during the intraoperative period and within the first 24 hours after surgery in the post-anesthesia care unit. Results: Surgeon satisfaction, intraoperative shoulder pain, postoperative pain after 2 h, and perioperative analgesic consumption (ketorolac) were significant better in group Magnesium than in group Bupivacaine. (P < 0.05). The onset of motor and sensory blocks was significant longer in group Magnesium than the other one. The incidence of PONV, pruritus and urinary retention was insignificant statistically between both groups. Conclusions: Magnesium sulfate if used intrathecally as an adjuvant to Bupivacaine would provide a better surgeon satisfaction and would improve the analgesic effect of spinal anesthesia used for gynecological laparoscopic surgery.

• The Korean Journal of Pain
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• 제22권1호
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• pp.68-73
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• 2009

Opioids profoundly inhibit evoked discharges of spinal nociceptive neurons, thereby inhibiting the transmission of pain. Intrathecal administration of opioids using implantable continuous infusion systems is an effective method of pain relief when other treatments have failed, as well as for patients with adequate analgesia on high dose therapy that produces unacceptable side effects. We report two cases of intrathecal pump implantation performed in patients suffering from intractable chronic pain. A test dose of 3 mg morphine was injected into the epidural space. No side effects were noted and patients experienced considerable pain relief. Implantation was performed one day after the test. The initial intrathecal morphine delivery dose was half of the equivalent dose of daily oral intake opioids and the infusion rate was increased gradually under close observation for opioid side effects. Two days post-implantation, both patients were discharged without any complications.

• The Korean Journal of Pain
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• 제23권4호
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• pp.230-235
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• 2010

Background: Bone cancer pain has a disruptive effect on the cancer patient's quality of life. Although ginsenosides have been used as traditional medicine in Eastern Medicine, the effect on bone cancer pain has not been throughly studied. The aim of this study was to determine whether ginsenosides may alter the bone cancer pain at the spinal level. Methods: NCTC 2472 tumor cells ($2.5{\times}10^5$) were injected into the femur of adult male C3H/HeJ mice to evoke bone tumor and bone cancer pain. To develop bone tumor, radiologic pictures were obtained. To assess pain, the withdrawal thereshold was measured by applying a von Frey filament to the tumor cells inoculation site. The effect of intrathecal ginsenosides was investigated. Effect of ginsenosides (150, 500, $1,000{\mu}g$) was examined at 15, 30, 60, 90, 120 min after intrathecal delivery. Results: The intrafemoral injection of NCTC 2472 tumor cells induced a radiological bone tumor. The withdrawal threshold with tumor development was significantly decreased compared to the sham animals. Intrathecal ginsenosides effectively increased the withdrawal threshold in the bone cancer site. Conclusions: NCTC 2472 tumor cells injection into the mice femur caused bone tumor and bone cancer pain. Intrathecal ginsenosides attenuated the bone cancer-related pain behavior. Therefore, spinal ginsenosides may be an alternative analgesic for treating bone cancer pain.

• Archives of Pharmacal Research
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• 제28권5호
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• pp.582-586
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• 2005

The present study was designed to characterize the possible roles of spinally located cholera toxin (CTX)- and pertussis toxin (PTX)-sensitive G-proteins in pro- inflammatory cy tokine induced pain behaviors. Intrathecal injection of tumor necrosis factor-a (TNF-${\alpha}$; 100 pg), interleukin-1${\beta}$ (IL-1${\beta}$ 100 pg) and interferon-${\gamma}$ (INF-${\gamma}$; 100 pg) showed pain behavior. Intrathecal pretreatment with CTX (0.05, 0.1 and 0.5 mg) attenuated pain behavior induced by TNF-${\alpha}$ and INF-${\gamma}$ administered intrathecally. But intrathecal pretreatment with CTX (0.05, 0.1 and 0.5${\mu}g$) did not attenuate pain behavior induced by IL-1${\beta}$. On the other hand, intrathecal pretreatment with PTX further increased the pain behavior induced by TNF-${\alpha}$ and IL-1${\beta}$ administered intrathecally, especially at the dose of 0.5 ${\mu}g$. But intrathecal pretreatment with PTX did not affect pain behavior induced by INF-${\gamma}$. Our results suggest that, at the spinal cord level, CTX- and PTX-sensitive G-proteins appear to play important roles in modulating pain behavior induced by pro-inflammatory cytokines administered spinally. Furthermore, TNF-${\alpha}$, IL-1${\beta}$ arid INF-${\gamma}$ administered spinally appear to produce pain behavior by different mechanisms.

• The Korean Journal of Pain
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• 제27권3호
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• pp.239-245
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• 2014

Background: Neuropathic pain induced by spinal or peripheral nerve injury is very resistant to common pain killers, nerve block, and other pain management approaches. Recently, several studies using stem cells suggested a new way to control the neuropatic pain. In this study, we used the spinal nerve L5 ligation (SNL) model to investigate whether intrathecal rat mesenchymal stem cells (rMSCs) were able to decrease pain behavior, as well as the relationship between rMSCs and reactive oxygen species (ROS). Methods: Neuropathic pain of the left hind paw was induced by unilateral SNL in Sprague-Dawley rats (n = 10 in each group). Mechanical sensitivity was assessed using Von Frey filaments at 3, 7, 10, 12, 14, 17, and 24 days post-ligation. rMSCs ($10{\mu}l$, $1{\times}10^5$) or phosphate buffer saline (PBS, $10{\mu}l$) was injected intrathecally at 7 days post-ligation. Dihydroethidium (DHE), an oxidative fluorescent dye, was used to detect ROS at 24 days post-ligation. Results: Tight ligation of the L5 spinal nerve induced allodynia in the left hind paw after 3 days post-ligation. ROS expression was increased significantly (P < 0.05) in spinal dorsal horn of L5. Intrathecal rMSCs significantly (P < 0.01) alleviated the allodynia at 10 days after intrathecal injection (17 days post-ligation). Intrathecal rMSCs administration significantly (P < 0.05) reduced ROS expression in the spinal dorsal horn. Conclusions: These results suggest that rMSCs may modulate neuropathic pain generation through ROS expression after spinal nerve ligation.