• 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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• 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.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2005년도 추계학술대회
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• pp.49-66
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• 2005

Panax ginseng has been useful for the treatment of diverse disease in oriental countries for thousands of years. In addition, a folk medicine prescribed by seven herbal drugs including Panax ginseng has been antinarcotics in the treatment of morphine-dependent patients. Many articles have been reported on these works. Therefore, we review the protective effects of Panax ginseng on the neurotoxicity induced by abuse drugs. Ginseng total saponins (GTS) extracted and isolated by Panax ginseng antagonized Morphine-induced analgesia, and inhibited the development of analgesic tolerance to and physical dependence on morphine. GTS inhibited morphine-6 dehydrogenase, which catalyzes production of mophinone from morphine, and increased hepatic glutathione level responsible to toxicity. Therefore, we hypothesized that these dual actions of ginseng can be associated with the detoxication of morphine. In addition, the inhibitory or facilitated effects of GTS on electrically evoked contraction in guinea pig ileum ($\mu$-receptors) and mouse vas deferens($\delta$-receptors) were not mediated through opioid receptors, suggesting non-opioid mechanisms. On the hand, antagonism of U-50,488H ($\kappa$-agonist)-induced antinociception is mediated by serotonergic mechanisms. GTS also inhibited hyperactivity, reverse tolerance (sensitization) and conditioned place preference-induced by psychostimulants such as methamphetamine, cocaine and morphine. On the other hand, GTS reduced the dopamine levels induced by methamphetamine. Moreover, GTS blocked the development of dopamine receptor activation, showing antidopaminergic effect. We suggest that GTS Prevent the methamphetamine-induced striatal dopaminergic neurotoxicity. In addition, Ginsenoside also attenuates morphine-induced cAMP signaling pathway. These results suggested that GTS might be useful for the therapy of the adverse actions of drugs with abuse liability.

• The Korean Journal of Physiology and Pharmacology
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• 제5권6호
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• pp.479-485
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• 2001

The existence of opioid receptors in mammalian cerebellum except human, has not been clearly understood. In the present study, we found that NPY was inducible by morphine in the mouse cerebellar granular and Purkinje cell layers. We performed in situ RT-PCR and immunohistochemistry to characterize the NPY expression. The increase of NPY gene expression by morphine (30 mg/kg, i.p.) was inhibited by pretreatment with not only naloxone (100 mg/kg, i.p.) but also a noncompetitive NMDA antagonist, MK-801 (0.3 mg/kg, i.p.). The competitive NMDA antagonist, AP-5 (0.9 mg/kg, i.p.) slightly attenuated the increased NPY expression by morphine. Also, the finding similar to morphine was shown by NMDA (70 mg/kg, i.p.) treatment. Our results indicate that NPY was inducible by morphine and this might reflect activation of NMDA receptors in granule cells that relay mossy fiber inputs to Purkinje cells via parallel fibers.

• Journal of Ginseng Research
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• 제14권2호
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• pp.178-186
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• 1990

The analgesic effect of morphine was antagonized and the development of tolerance was suppressed by the modification of the neurologic function in the animals treated with ginseng saponins The activation of the spinal descending inhibitory systems as well as the supraspinal structures by the administration of morphine was inhibited in the animals treated with ginseng saponine intracerebrally or intrathecally. The development of morphine tolerance and dependence, and the abrupt expression of naloxone inducted abstinence syndrom were also inhibited by ginsenoside Rb1, Rb2, Rg1 and Re. These results suggest that ginsenoside Rbl, Hbs, Rgl and Re are the bioactive components of panax ginseng on the inhibition of the development of morphine tolerance and dependence, and the inhibition of abrupt abstinence sindrome. In addition, further research on the minor components of Pnnnxkinsenl should be investigated. A single or daily treatment with ginseng saponins did not induce any appreciable changes in the brain in level of monoamines at the variolls time intervals and at the various day intervals, respectively. The inhibitory or facilitated effects of ginseng saponins on electrically evoked contractions in guinea pig ileum ($\mu$-receptor) and mouse vats deferens ($\delta$-receptor) were not mediated through opioid receptors. The antagonism of a $\chi$ receptor agonist, U-50, 488H was also not mediated through opioid receptors in the animals treated with ginseng saponins, but mediated through serotonergic mechanisms. Ginseng saponins inhibited morphine 6-dehydrogenase which catalyzed the production of morphinone from morphine, and increased hepatic glutathione contents for the detoxication of morphinone. This result suggests that the dual action of the above plays an important role in the inhibition of the development of morphine tolerance and dependence.

• The Korean Journal of Pain
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• 제7권1호
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• pp.1-12
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• 1994

• 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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• 제33권2호
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• pp.183-191
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• 2020

Background: Opioids can present intolerable adverse side-effects to patients who use these analgesics to mitigate chronic pain. In this retrospective analysis, cooled radiofrequency (CRF) denervation was evaluated to provide pain and disability relief and reduce opioid use in patients with sacroiliac joint (SIJ) derived low back pain (LBP). Methods: Twenty-seven patients with pain from SIJ refractory to conservative treatments, and taking opioids chronically (> 3 mo), were included. Numeric rating scale (NRS) and Oswestry disability index (ODI) scores were collected at 1, 6, and 12 months post-procedure. Opioid use between baseline and each follow-up visit was compared for the entire group and for those who experienced successful (pain reduction ≥ 50% of baseline value) or unsuccessful CRF denervation. Results: Severe initial mean pain (NRS score: 7.7 ± 1.0) and disability (ODI score: 50.1 ± 9.0), and median opioid use (morphine equivalent daily dose: 40 ± 37 mg) were significantly reduced up to 12 months post-intervention. CRF denervation was successful in 44.4% of the patients at 12 months. Regardless of procedure success, patients demonstrated similar opioid reductions and changes in opioid use at 12 months. Two patients (7.4%) experienced neuritis following CRF denervation. Conclusions: CRF denervation of the SIJ can safely elicit pain and disability relief, and reduce opioid use, regardless of intervention success. Future studies may support CRF denervation as a dependable therapy to alleviate opioid use in patients with SIJ-derived LBP and show that opioid use measurements can be a surrogate indicator of pain.

• Archives of Pharmacal Research
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• 제18권2호
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• pp.113-117
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• 1995

We re-cloned mouse ${\delt}-Opioid$receptor from NG108-15 cells using RT-PCR, and confirmed it by restriction analysis and by sequencing the beginning and end part of the amplified DNA. When transiently expressed in COS-7 cells, cloned ${\delt}-Opioid$ receptor showed saturable and specific binding to $[^3H]$naloxone with very similar binding parameters to originally reported ones. To make antibodies specific for the ${\delt}-Opioid$ receptor, the carboxy tail of the receptor, which is unique to the ${\delt}-Opioid$ receptor compared with other opioid receptors, was expressed in bacteria as a ufsion proteinwith glutathione S-transferase. Purified fusion protein selective for ${\delt}-Opioid$ receptor when tested by western blotting using membrane proteins prepared from transfected COS-7 cells. Cloned ${\delt}-Opioid$ receptor andl antibodies specific for ${\delt}-Opioid$ receptor are going to be valuable tools for studying pharmacological actions of the ${\delt}-Opioid$ receptor and morphine dependence.

• Journal of Hospice and Palliative Care
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• 제26권1호
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• pp.18-21
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• 2023

The combination of oxycodone and naloxone is useful for cancer pain management. Naloxone, as a pure opioid antagonist, cannot be used simultaneously with opioids. However, owing to its low bioavailability, it can be used in an oral composite formulation. We present the case of a 55-year-old man with gastric cancer who experienced severe opioid withdrawal syndrome (OWS) triggered by oxycodone/naloxone that was successfully managed with dexmedetomidine. He had been in a stable condition on intravenous morphine to alleviate cancer pain. Intravenous morphine was switched to oral oxycodone/naloxone for discharge from the hospital. The patient suddenly developed restlessness, heartburn, and violent behavior 30 minutes after taking oxycodone/naloxone. We attempted sedation with midazolam and propofol, but paradoxical agitation and desaturation occurred. Next, we tried dexmedetomidine and the patient showed a decreased heart rate and reduced agitation. The patient was eventually stabilized by increasing the dose of dexmedetomidine. This report informs clinicians of the possibility of OWS when switching from opioids to oxycodone/naloxone, which can be overcome with the appropriate use of sedatives and dexmedetomidine depending on the patient's condition.