• The Korean Journal of Pain
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• 제6권1호
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• pp.32-39
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• 1993

전북대학교 병원에 입원하여 하복부 수술을 받는 미국 마취과학회 전신상태 분류상 class I, II인 환자 40명을 대상으로 수술후 morphine(1군)과 ketorolac(2군)을 지속적으로 정주한 결과 다음과 같은 결론을 얻었다. 1) 1군과 2군 모두 수술후 통증에 의의 있는 감소를 보였으며 군 간의 차이는 없었다. 2) 1군에서 2군보다 부작용의 빈도가 많았다. 이상의 결과로 수술후 통증 관리에 있어서 morphine과 ketorolac의 지속적 정맥 주입 방법은 모두 효과적이었으며, ketorolac이 morphine보다 부작용의 발현 빈도가 더 적은것으로 보아 morphine을 대신할 수 있는 유용한 약물로 사료된다.

• The Korean Journal of Pain
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• 제37권3호
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• pp.233-246
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• 2024

Background: Ferrostatin-1 and liproxstatin-1, both ferroptosis inhibitors, protect cells. Liproxstatin-1 decreases morphine tolerance. Yet, ferrostatin-1's effect on morphine tolerance remains unexplored. This study aimed to evaluate the influence of ferrostatin-1 on the advancement of morphine tolerance and understand the underlying mechanisms in male rats. Methods: This experiment involved 36 adult male Wistar albino rats with an average weight ranging from 220 to 260 g. These rats were categorized into six groups: Control, single dose ferrostatin-1, single dose morphine, single dose ferrostatin-1 + morphine, morphine tolerance (twice daily for five days), and ferrostatin-1 + morphine tolerance (twice daily for five days). The antinociceptive action was evaluated using both the hot plate and tail-flick tests. After completing the analgesic tests, tissue samples were gathered from the dorsal root ganglia (DRG) for subsequent analysis. The levels of glutathione, glutathione peroxidase 4 (GPX4), and nuclear factor erythroid 2-related factor 2 (Nrf2), along with the measurements of total oxidant status (TOS) and total antioxidant status (TAS), were assessed in the tissues of the DRG. Results: After tolerance development, the administration of ferrostatin-1 resulted in a significant decrease in morphine tolerance (P < 0.001). Additionally, ferrostatin-1 treatment led to elevated levels of glutathione, GPX4, Nrf2, and TOS (P < 0.001), while simultaneously causing a decrease in TAS levels (P < 0.001). Conclusions: The study found that ferrostatin-1 can reduce morphine tolerance by suppressing ferroptosis and reducing oxidative stress in DRG neurons, suggesting it as a potential therapy for preventing morphine tolerance.

• The Korean Journal of Pain
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• 제18권2호
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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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• 제7권1호
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• pp.78-83
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• 1994

수술후 통증치료에 morphine과 buprenorphine의 효과를 알아보기 위하여 morphine과 buprenorphinec을 단독 투여하거나(1, 2군) buprenorphine과 ketorolac을 반량씩 혼합하여 지속적으로 정주(3군)하여 다음과 같은 결과를 얻었다. 1) 각군에서 모두 혈압과 맥박의 의의있는 변화는 초래하지 않았다. 2) Visual analogue scale으로 평가한 진통 발현은 각군에서 모두 비슷하였다. 3) Visual analogue scale과 Prince Henry Scale로 평가한 진통효과는 morphine군에서 가장 우수하였고, buprenorphine군과 buprenorphine+ketorolac의 반량 투여군에서는 비슷하였다. 4) 부작용의 발생은 1군과 2군에서 비슷하였으나 3군에서 가장 낮았다. 이상의 결과로 보아 지속적 정주에 의한 술후 통증의 억제에 있어서 buprenorphine은 morphine을 대치할 수는 있으나 morphine보다 우수하지는 못한 것으로 사료되며, buprenorphine 사용시는 ketorolac을 병용하여 사용량을 줄염으로써 부작용을 줄일 수 있을 것으로 사료된다.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 1990년도 Proceedings of International Symposium on Korean Ginseng, 1990, Seoul, Korea
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• pp.36-44
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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 saponins intracerebrally or intrathecally The development of morphine tolerance and dependence, and the abrupt expression of naloxone induced abstinence syndrome were also inhibited by ginsenoside Kbl , Rba, Rgl and Re. These results suggest that ginsenoside Kbl, Rba, 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 syndrome. In addition, further research on the minor components of Panax ginseng should be investigated. A single or daily treatment with ginseng saponins did not induce any appreciable changes in the brain level of monoamines at the various 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 (U-receptor) and mouse was definers (5·receptor) were not mediated through opioid receptors. The antagonism of a x receptor agonist, U-, iO.488H was also not mediated through opioid receptors in the animals treated with ginseng saponins, bolt mediated through serotonergic mechanisms. Ginseng saponins inhibited morphine S-dehydrogenase that catalyzed the production of morphine from morphine, and increased hepatic glutathione contents for the detoxification of morphine. 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.

• 대한약리학회지
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• 제16권2호
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• pp.1-7
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• 1980

As it has been reported that morphine induce antidiuresis, and antinatriuresis along with decrease in renal hemodynamics when given intracerebroventricularly[ivt], the renal action of nalorphine, a partial antagonist of morphine action, and its influence upon the morphine action were investigated in this study. $10{\mu}g/kg$ of nalorphine given into the lateral ventricle of the rabbit brain tended to decrease renal plasma flow and glomerular filtration rate and increase the reabsorption of free water in the tubules. $100{\mu}g/kg$ ivt significantly decreased urine flow rate and increased free water reabsorption, and tended to increase electrolyte excretion in spite of decrease in renal plasma flow and glomerular filtration, suggesting that ADH also involved in the antidiuresis. Morphine hydrochloride, $10{\mu}g/kg$, ivt, produced marked decrement in renal hemodynamics along with decreased excretions of sodium, potassium and water, and these morphine actions were alleviated by nalorphine given 20 min later. The natriuretic action of ivt nalorphine manifested itself uninfluenced by the morphine. These observations indicate that nalorphine ivt produces renal actions similar to those of morphine, though less potent, and that it can antagonize the latter action. It is suggested that morphine influences renal hemodynamics through nerve by stimulating the 'morphine receptor' in the brain, whereas nalorphine liberates ADH by the agonistic action on the 'nalorphine receptor'.

• The Korean Journal of Pain
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• 제10권2호
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• pp.191-195
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• 1997

Backgound: The present study was undertaken to determine whether fentanyl or bupivacaine is a better adjuvant to epidural morphine with respect to postoperative analgesic use and with fewer incidence of side effects. Methods: We evaluated the clinical effects in 62 patients having cesarean section, divided in 3groups randomly. Group I(n=19) was received epidural morphine 4 mg, group II(n=22) was received epidural morphine 2 mg plus fentanyl 50 ${\mu}g$ and group III(n=21) was received morphine 2 mg plus 0.25% bupivacaine 10 ml epidurally. We measured the first request time of analgesic for postoperative pain, the number of supplemental analgesics within 24 hours and the incidence of side effects postoperatively. Results: The first request time of analgesic for postoperative pain was significantly shorter in group III than in group I and II. The analgesic use in the first 24 hours was significantly more in group III than in group I and II. The side effects were significantly fewer incidence in group II than in group I and III. Conclusions: In conclusion, the combined use of epidural morphine and fentanyl provided better analgesia than the combined of epidural morphine and bupivacaine.

• The Korean Journal of Pain
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• 제2권2호
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• pp.189-193
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• 1989

The analgesic effects of epidural morphine were evaluated on various types of cancer-related pain in forty-eight adult patients. Epidural morphine injections were given via an epidural catheter introduced to an epidural level corresponding to the pain area. Pain relief was classified as excellent, fair, or poor by subjective scoring and by the subsequent need for systemic analgesics. Thirty-two patients of all the patients became pain-free. In sixteen patients, pain relief was complete only for one or two of various types of pain with a certain dose of epidural morphine, The best result was obtained when the pain was continuous and originated from deep somatic structures. Based on the results, the ranking order of different types of cancer pain with regard to their susceptibility to epidural morphine was as follows: 1) Continuous somatic pain 2) Continuous visceral pain 3) Intermittent somatic pain 4) Intermittent visceral pain The differential effects of epidural morphine on cancer-related pain may suggest that various types of noxious stimuli involve different kinds of opioid receptors which differ in affinity to morphine, and that there are some pain-mediating systems which function independently of opioid mechanisms.

• Journal of Ginseng Research
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• 제40권4호
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• pp.445-452
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• 2016

Background: Red ginseng and ginsenosides have shown plethoric effects against various ailments. However, little is known regarding the effect of red ginseng on morphine-induced dependence and tolerance. We therefore investigated the effect of red ginseng extract (RGE) and biotransformed ginsenosides Rh2, Rg3, and compound K on morphine-induced dependence in mice and rats. Methods: While mice were pretreated with RGE and then morphine was injected intraperitoneally, rats were infused with ginsenosides and morphine intracranially for 7 days. Naloxone-induced morphine withdrawal syndrome was estimated and conditioned place preference test was performed for physical and psychological dependence, respectively. Western blotting was used to measure protein expressions. Results: Whereas RGE inhibited the number of naloxone-precipitated jumps and reduced conditioned place preference score, it restored the level of glutathione in mice. Likewise, ginsenosides Rh2, Rg3, and compound K attenuated morphine-dependent behavioral patterns such as teeth chattering, grooming, wet-dog shake, and escape behavior in rats. Moreover, activated N-methyl-D-aspartate acid receptor subunit 1 and extracellular signal-regulated kinase in the frontal cortex of rats, and cultured cortical neurons from mice were downregulated by ginsenosides Rh2, Rg3, and compound K despite their differential effects. Conclusion: RGE and biotransformed ginsenosides could be considered as potential therapeutic agents against morphine-induced dependence.

• The Korean Journal of Physiology and Pharmacology
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• 제16권6호
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• pp.379-386
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• 2012

The purpose of this study was to evaluate whether berberine (BER) administration could attenuate depression- and anxiety-like behaviors and increase corticotrophin-releasing factor (CRF) and tyrosine hydroxylase (TH) expression following chronic morphine withdrawal in rats. Male rats were exposed to chronic, intermittent, escalating morphine (10~50 mg/kg) for 10 days. After the last morphine injection, depression- and anxiety-like beahvior associated with morphine discontinuation persisted for at least three days during withdrawal without any change in ambulatory activity. Daily BER administration significantly decreased immobility in the forced swimming test and increased open-arm exploration in the elevated plus maze test. BER administration also significantly blocked the increase in hypothalamic CRF expression and TH expression in the locus coeruleus (LC) and the decrease in hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression. Taken together, these findings demonstrated that BER administration significantly reduced morphine withdrawal-associated behaviors following discontinuation of repeated morphine administration in rats, possibly through modulation of hypothalamic CRF and the central noradrenergic system. BER may be a useful agent for treating or alleviating complex withdrawal symptoms and preventing morphine use relapses.