• The Korean Journal of Pain
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• 제19권2호
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• pp.131-136
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• 2006

Background: The aim of this study was to clarify the role of spinal groups II and III metabotropic glutamate receptors (mGluRs) with respect to postoperative pain at the spinal level. In addition, the nature of the pharmacological interaction between groups II and III mGluRs agonists and morphine was determined. Methods: Catheters were inserted into the intrathecal space of male SD rats. To induce postoperative pain, an incision was made in the plantar surface of the hind paw. A pharmacological characteristic for the interaction between groups II and III mGluRs agonists and morphine was evaluated using a fixed-dose analysis. Results: None of intrathecal group II and III mGluRs agonists modified the withdrawal threshold of the incisional pain. The administration of intrathecal morphine resulted in an increase of a dose dependent withdrawal threshold. A fixed-dose analysis revealed that the group III mGluRs agonist, ACPT-III, increased the antinociceptive action of morphine, while the group II mGluRs agonist, APDC, had no effect the antinociception of morphine. Conclusions: These results suggest that group II and III mGluRs may not play a direct modulatory role in the processing of postoperative pain at the spinal level. However, agonizing group III mGluRs may indirectly contributable to the potentiation of morphines antinociception in the spinal cord. Thus, the combination of morphine and a group III mGluRs agonist may be useful in the management of spinal postoperative pain.

• The Korean Journal of Pain
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• 제18권1호
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• pp.1-9
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• 2005

Background: Spinal metabotropic glutamate receptors (mGluRs) and opioid receptors are involved in the modulation of nociception. Although opioid receptors agonists are active for pain, the effects of the compounds for the mGluRs have not been definitely investigated at the spinal level. We examined the effects of the intrathecal mGluR compounds and morphine in the nociceptive test, and then we further clarified the role of the spinal mGluRs. In addition, the nature of the pharmacological interaction after the coadministration of mGluRs compounds with morphine was determined. Methods: Catheters were inserted into the intrathecal space of male SD rats. For the induction of pain, $50{\mu}l$ of 5% formalin solution or a thermal stimulus was applied to the hindpaw. An isobolographic analysis was used for the evaluation of the drug interaction. Results: Neither group I mGluR compounds nor group III mGluR compounds produced any antinociceptive effect in the formalin test. The group II mGluR agonist (APDC) had little effect on the formalin-induced nociception. The group II mGluR antagonist (LY 341495) caused a dose-dependent suppression of the phase 2 flinching response on the formalin test, but it did not reduce the phase 1 response of the formalin test nor did it increase the withdrawal latency of the thermal stimulus. Isobolographic analysis revealed a synergistic interaction after the intrathecal delivery of a LY 341495-morphine mixture. Conclusions: These results suggest that group II mGluRs are involved in the facilitated processing at the spinal level, and the combination of LY 341495 with morphine may be useful to manage the facilitated pain state.

• The Korean Journal of Pain
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• 제12권1호
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• pp.59-63
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• 1999

Background: Contraction of anal sphincter muscle produces severe pain in perianal surgery postoperatively. Recent reports have indicated that effective and prolonged pain relief can be obtained by the injection of small doses of morphine into the subarachnoid space. We attempted to use this technique for perianal surgery and investigated postoperative pain control and its side effects. Methods: Forty five patients scheduled for hemorrhoidectomy and anal fistulectomy were studied to determine the minimal effective dose of intrathecal morphine for postoperative analgesia. In order to control the pain, 7 mg of 0.5% hyperbaric bupivacaine with 0.05 mg (group I), 0.1 mg (group II) and 0.15 mg (group III) of morphine hydrochloride was injected with a 25 gauge spinal needle into the subarachnoid space. We estimated the duration of analgesia until the pain score attained to above 3 in 10 cm VAS (visual analogue scale) and incidence of itching, nausea and vomiting by percentage, headache, backpain and respiratory depression by positive and negative. We also checked the time of self-voiding. Results: The mean time of analgesia was $10.3{\pm}1.54$, $19.7{\pm}2.22$ and $20.3{\pm}2.29$ hours in group I, II and III respectively. Urinary retention of group I, II and III after block persisted for an average of $20.3{\pm}2.31$, $21.2{\pm}2.51$ and $23.3{\pm}3.74$ hours. Nausea and vomiting were observed 33%, 53%, 67% and itching was observed 53%, 67%, 80% in group I, II and III respectively and respiratory depression did not occur in all groups. Conclusions: It is not necessary to use more than 0.1mg of intrathecal morphine in perianal surgery because analgesia is not prolonged and side effects are increased.

• The Korean Journal of Pain
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• 제26권1호
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• pp.14-20
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• 2013

Background: Nefopam, a non-opiate analgesic, has been regarded as a substance that reduces the requirement for morphine, but conflicting results have also been reported. The inhibition of monoamine reuptake is a mechanism of action for the analgesia of nefopam. The spinal cord is an important site for the action of monoamines however, the antinociceptive effect of intrathecal nefopam was not clear. This study was performed to examine the antinociceptive effect of intrathecal (i.t.) nefopam and the pattern of pharmacologic interaction with i.t. morphine in the formalin test. Methods: Male Sprague-Dawley rats were implanted with an i.t. catheter, and were randomly treated with a vehicle, nefopam, or morphine. Formalin was injected into the hind-paw 10 min. after an i.t. injection of the above experiment drugs. After obtaining antinociceptive $ED_{50}$ of nefopam and morphine, the mixture of nefopam and morphine was tested for the antinociceptive effect in the formalin test at a dose of 1/8, 1/4, 1/2 of $ED_{50}$, or $ED_{50}$ of each drug followed by an isobolographic analysis. Results: Intrathecal nefopam significantly reduced the flinching responses in both phases of the formalin test in a dose-dependent manner. Its effect, however, peaked at a dose of $30{\mu}g$ in phase 1 (39.8% of control) and $10{\mu}g$ during phase 2 (37.6% of control). The isobolograhic analysis indicated an additive interaction of nefopam and morphine during phase 2, and a synergy effect in antinociception during phase 1. Conclusions: This study demonstrated that i.t. nefopam produces an antinociceptive effect in formalin induced pain behavior during both phases of the formalin test, while interacting differently with i.t. morphine, synergistically during phase 1, and additively during phase 2.

• The Korean Journal of Pain
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• 제25권1호
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• pp.47-51
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• 2012

Intrathecal drug administration system (ITDAS) can reduce the side effects while increasing the effectiveness of opioids compared to systemic opioid administration. Therefore, the use of ITDAS has increased in the management of cancer pain and chronic intractable pain. Catheter obstruction is a serious complication of ITDAS. Here, we present a case of catheter obstruction by a mass formed at the side hole and in the lumen. A 37-year-old man suffering from failed back surgery syndrome received an ITDAS implantation, and the ITDAS was refilled with morphine every 3 months. When the patient visited the hospital 18 months after ITDAS implantation for a refill, the amount of delivered morphine sulfate was much less than expected. Movement of the pump rotor was examined with fluoroscopy; however, it was normal. CSF aspiration through the catheter access port was impossible. When the intrathecal catheter was removed, we observed that the side hole and lumen of the catheter was plugged.

• The Korean Journal of Pain
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• 제18권2호
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• pp.113-117
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• 2005

Background: Serotonin 3 receptor is involved in the modulation of nociceptive transmission in the spinal cord. The serotonin 3 receptor antagonist has been used for the management of opioid-induced nausea and vomiting. The aim of this study was to examine whether the analgesic effect of morphine is antagonized by serotonin 3 receptor antagonists at the spinal level. Methods: Rats were implanted with lumbar intrathecal catheters. For nociception, a formalin solution (5%, $50{\mu}l$) was injected into the hind paw of male Sprague-Dawley rats. To determine whether the effect of intrathecal morphine was mediated via serotonin 3 receptors, serotonin 3 receptor antagonists were intrathecally administered 10 min prior to the morphine delivery. Following the formalin injection, formalin-induced nociceptive behavior (flinching response) was observed for 60 min. Results: Intrathecal morphine produced a dose-dependent suppression of the flinches in both phases during the formalin test. The analgesic action of morphine was not reversed by serotonin 3 receptor antagonists (LY-278,584, ondansetron), which had little per se effect on the formalin-induced nociception. Conclusions: Spinal serotonin 3 receptors may not be involved in the analgesia of morphine on a nociceptive state evoked by a formalin stimulus.

• The Korean Journal of Pain
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• 제5권1호
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• pp.69-75
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• 1992

The author experienced of four patients with intractable pain who were treated by continuous intraventricular infusion of morphine through an implanted port system. One suffered from tongue cancer and the others from bone metastasis or distant metatasis of abdominal cancer which were ineffectively to managed through an epidural route. Our experience is that this is a safe and effective method of pain management in patients with head and neck cancer. It is useful as well in patients who have intractable pain that cannot be managed through an intrathecal or epidural route.

• 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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• 제27권2호
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• pp.139-144
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• 2014

Background: To manage intractable cancer pain, an alternative to systemic analgesics is neuraxial analgesia. In long-term treatment, intrathecal administration could provide a more satisfactory pain relief with lower doses of analgesics and fewer side-effects than that of epidural administration. However, implantable drug delivery systems using intrathecal pumps in Korea are very expensive. Considering cost-effectiveness, we performed epidural analgesia as an alternative to intrathecal analgesia. Methods: We retrospectively investigated the efficacy, side effects, and complications of epidural morphine and local anesthetic administration through epidural catheters connected to a subcutaneous injection port in 29 Korean terminal cancer patients. Patient demographic data, the duration of epidural administration, preoperative numerical pain rating scales (NRS), side effects and complications related to the epidural catheterization and the drugs, and the numerical pain rating scales on the 1st, 3rd, 7th and 30th postoperative days were determined from the medical records. Results: The average score for the numerical pain rating scales for the 29 patients decreased from $7{\pm}1.0$ at baseline to $3.6{\pm}1.4$ on postoperative day 1 (P < 0.001). A similar decrease in pain intensity was maintained for 30 days (P < 0.001). Nausea and vomiting were the most frequently reported side effects of the epidural analgesia and two patients (6.9%) experienced paresthesia. Conclusions: Epidural morphine and local anesthetic infusion with a subcutaneous pump seems to have an acceptable risk-benefit ratio and allows a high degree of autonomy to patients with cancer pain.

• Journal of Ginseng Research
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• 제23권4호
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• pp.239-246
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• 1999

백서를 이용하여 진세노사이드 흑은 모르핀을 척수강내 투여한 다음 tail-flick test를 통하여 진통 작용을 연구하였다. 또한, 진세노사이드를 모르핀과 함께 척수강내 장기 처리할 경우 모르핀에 의한 내성 및 의존성 유발에 미치는 영향을 연구하였다. 연구 결과, 척수강내 진세노사이드의 투여는 200 ${\mu}g$/rat에서 약한 진통 작용이 있는 것으로 나타났다. 모르핀은 투여 농도에 의존적으로 좋은 진통 효능을 보여주었으며, $ED_50$은 1.2 ${\mu}g/rat$인 것으로 나타났다. 그러나 진세노사이드의 모르핀을 함께 척수강내 투여할 경우 모르핀의 진통 작용을 증가 시키지 않은 것으로 나타났다. 200 ug/rat 진세노사이드를 10 ${\mu}g$/rat모르핀을 7일 동안 같이 투여할 경우 모르핀에 의한 통증 작용에 대한 내성을 억제하였으며, 모르핀에 의한 의존성을 부분적으로 억제하는 것으로 나타났다. 이러한 연구 결과는 척수 수준에서 진세노사이드가 모르핀의 장기 투여에 의하여 유도되는 모르핀에 대한 내성 및 의존성을 억제하는 것으로 사료된다.