• 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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• 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.

• Journal of Hospice and Palliative Care
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• 제5권1호
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• pp.24-30
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• 2002

배경 : 통증은 암 환자에서 가장 두려운 증상중의 하나이다. 암 환자의 $65{\sim}85%$가 통증을 경험하였고, 이들 환자에게 때에 따라서는 고용량의 몰핀이 사용되기도 한다. 그러나 많은 의사들은 아직까지 몰핀에 대한 두려움을 가지고 있어, 고용량의 몰핀을 쓰는 데 주저하고 있다. 이에 저자 등은 말기 암 환자에서 몰핀 사용에 대한 실태조사를 통해 몰핀 용량에 따른 차이가 있는지 여부를 알아보고자 하였다. 방법 : 2000년 7월 1일부터 2001년 12월 31일까지 경기도 고양시 소재 일개 종합병원 가정의학과에 입원하여 1주일 이상 생존하였다가 임종한 암 환자 99명을 대상으로 환자의 인구통계학적인 자료 임상 병리 검사, 몰핀 사용 용량 등을 조차하였다. 몰핀은 사용 용량에 따라 OME(oral morphine equivalent)로 계산하여 150 mg이하면 저용량으로 150 mg 초과면 고용량 군으로 나누어, 나이, 성별, 암의 종류, 전이 여부, 몰핀의 부작용 등의 측면에서 두 군간의 차이가 있는 지를 ch-square test를 통해 분석하였다. 결과 : 평균 연령에서는 저용량군이 $65.0{\pm}13.1$세, 고용량군이 $59.9{\pm}11.6$세였고, 성별은 저용량군이 남자 32명(50.0%), 여자 32명(50.0%), 고용량군은 남자 15명(51.7%), 여자 14명(48.3%)이었다. 암의 종류를 보면 두 군 다 위암이 제일 많았고, 그 다음으로 폐암 순이었다. 전이 여부에서는 저용량군 중 58명(90.6%), 고용량군 중 28명(96.6%)에서 전이가 있었다. 기타 완화적 목적의 방사선 치료나 부작용 측면에서 두 군간의 차이는 없었다. 결론 : 암 환자에서 임종 1주일 동안 몰핀 용량에 따른 차이는 없었다. 그러므로 말기 암환자를 치료하는데 있어 고용량 몰핀 사용을 주저할 필요는 없다.

• The Korean Journal of Pain
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• 제35권1호
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• pp.66-77
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• 2022

Background: Thrombospondin-4 (TSP4) upregulates in the spinal cord following peripheral nerve injury and contributes to the development of neuropathic pain (NP). We investigated the effects of cyanocobalamin alone or in combination with morphine on pain and the relationship between these effects and spinal TSP4 expression in neuropathic rats. Methods: NP was induced by chronic constriction injury (CCI) of the sciatic nerve. Cyanocobalamin (5 and 10 mg/kg/day) was administered 15 days before CCI and then for 4 and 14 postoperative days. Morphine (2.5 and 5 mg/kg/day) was administered only post-CCI. Combination treatment included cyanocobalamin and morphine, 10 and 5 mg/kg/day, respectively. All drugs were administered intraperitoneally. Nociceptive thresholds were detected by esthesiometer, analgesia meter, and plantar test, and TSP4 expression was assessed by western blotting and fluorescence immunohistochemistry. Results: CCI decreased nociceptive thresholds in all tests and induced TSP4 expression on the 4th postoperative day. The decrease in nociceptive thresholds persisted except for the plantar test, and the increased TSP4 expression reversed on the 14th postoperative day. Cyanocobalamin and low-dose morphine alone did not produce any antinociceptive effects. High-dose morphine improved the decreased nociceptive thresholds in the esthesiometer when administered alone but combined with cyanocobalamin in all tests. Cyanocobalamin and morphine significantly induced TSP4 expression when administered alone in both doses for 4 or 14 days. However, this increase was less when the two drugs are combined. Conclusions: The combination of cyanocobalamin and morphine is more effective in antinociception and partially decreased the induced TSP4 expression compared to the use of either drug alone.

• Journal of Hospice and Palliative Care
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• 제11권3호
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• pp.136-139
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• 2008

목적: 경막외 모르핀 주입을 시행 받은 호스피스 병동의 암환자에서 통증 조절의 효율성과 안전성, 합병증에 대해 알아보고자 하였다. 방법: 2001년 3월부터 2004년 3월까지 3년간 성빈센트병원 호스피스 병동에 입원한 환자 중 경막외 모르핀 주입을 시행한 24명에 대해 환자의 일반 특성과 모르핀 등가용량, 기저 질환, 도관의 거치기간 등에 대해 후향 적으로 자료 분석하였다. 결과: 환자들은 위암, 췌장암이 각각 5명으로 가장 많았으며 경막외 모르핀 주입 부위는 흉추가 15명으로 가장 많았다. 시행 당시의 기저 모르핀 등가 용량(morphine equivalent daily dose, MEDD)은 615 mg이었다. 경막외 모르핀 주입을 시행 받고 1주일 뒤의 MEDD는 274 mg으로 효과적인 통증 조절이 가능하였다(P-value=0.000). 경막외 도관을 제거한 환자는 6명으로 이중 3명은 재 삽입하였다. 도관의 감염으로 인하여 제거한 환자는 2명이었다. 결론: 호스피스 병동에서 시행한 경막외 지속적 모르핀 주입은 진행한 암 환자의 통증 조절에 효율적이었으며 도관의 위치 변동, 감염으로 인하여 제거한 경우가 있었으나 조절 가능한 합병증이었다. 다만 1일 주사용 모르핀 요구량이 100 mg일 때 경막하 모르핀 주입법을 통한 통증 조절을 권하더라도 동의를 얻는데 걸리는 기간 중 기저 질환의 악화 등으로 인한 투여 모르핀 용량의 증량으로 경막외 모르핀 주입 당시 평균 MEDD는 615 mg이었다. 향후 환자 및 보호자들에게 경막외 모르핀 주입의 효율성과 안전성에 대한 정보 제공이 필요할 것으로 생각한다.

• The Korean Journal of Pain
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• 제19권1호
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• pp.96-100
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• 2006

Pain control is very important in managing terminal cancer patients and there are several modalities to alleviate their pain. A high dosage of epidural morphine is effective to control terminal cancer pain. Furthermore, to decrease the amount of morphine, adding an alternative adjuvant like ketamine to the morphine regimen is considered helpful for controlling the pain of a terminal cancer patient. A 45 year old male patient with terminal lung cancer had neck pain that was caused by multiple bone metastases. Continuous epidural block was started with 2 mg/day of morphine and the dosage was gradually increased to 90 mg/day in 86 days. 30 mg/day of ketamine was then added to it. Overall, the morphine and ketamine dosages were increased to 564 mg/day and 140 mg/day, respectively, in 11 months until the patient expired. In this case, the high dosage of epidural morphine, 580 mg/day, was administered to control cancer pain without any severe adverse effects.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.294-294
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• 1994

To investigate analgesic mechanism of capsaicin and its analogues (capsaicinoids), release of adenosine was measured by high performance liquid chromatography from dorsal spinal cord synaptosomes, Exposure of synaptosomes to K$\^$+/ and morphine produced a dose dependent release of adenosine in the presence of Ca$\^$++/. Capsaicin (0.1, 1, 10 M), and its analogues 6-paradol (1, 10 M), NE-19550 (1, 10, 100 M), DMNE (1, 10, 100 M) and KR 25018 (0.1, 1, 10 M) produced a dose dependent release of adenosine in the presence of Ca$\^$++/. Nifedipine, L-type voltage sensitive calcium channel blocker, inhibited K$\^$+/ (6, 12 mM)- and morphine (10 M)-evoked release of adenosine completely, but inhibited capsaicin, and capsaicinoids-evoked release of adenosine partially. Capsazepine, a novel capsaicin select ive antagonist, blocked only capsaicin and capsaicinoids induced release of adenosine. Therefore, the adenosine release by capsaicin and capsaicinoids having antinociceptive effects involve activation of capsaicin specific receptor and capsaicin sensitive Ca$\^$++/ channel.

• The Korean Journal of Pain
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• 제10권2호
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• pp.170-178
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• 1997

Background: The analgesic efficacy and safety of propacetamol, an injectable prodrug of acetoaminophen, in combination with intravenous morphine PCA were studied in 40 patients after gynecological surgery requiring lower abdominal incision. Methods: Using a double-blind, randomized, parallel-group design, the effects of four(every 6 hr) intravenous injections of 2 g propacetamol(=1 g acetoaminophen) were compared with four injections of placebo(PL) immediately after surgery. Efficacy of cumulative dose of morphine and number of boluses requested was assessed over 24 hours by automated recording on the PCA device. It was assessed on pain scores rated on a ten-point verbal scale along with vital signs, $K^+$, glucose, BUN, creatinine, PT and PTT were measured along with stress hormones(epinephrine, norepinephrine and cortisol). Results: There were no differences in demographic data between two groups. Propacetamol group demonstrated approximately 21% morphine sparing effect compared to placebo group($33.1{\pm}10.4$ mg vs $41.4{\pm}8.0$ mg). No significant differences noted in $K^+$, glucose, BUN, Creatinine, PT and PTT levels. There were significant increases in norepinephrine and cortisol in placebo group postoperatively, compared to preoperative values. At the same time, propacetamol group also showed significant changes in these hormones. Both group revealed high degree of patient satisfaction. Conclusion: Propacetamol showed significant morphine sparing effect to some degree. Side effects were much less in propacetamol group with subsequently high patient satisfaction. The secretion of stress hormone were not blocked by postoperative propacetamol injections. Authors concluded that propacetamol should be considered as an excellent adjuvant analgesics in postoperative pain control in opioid patient controlled analgesia.

• The Korean Journal of Pain
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• 제6권2호
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• pp.213-219
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• 1993

수술후 통증관리에 있어서 경막외 buprenorphine의 유용성을 알아보기 위하여 상복부 수술을 받은 환자에 있어서 morphine 2 mg 및 4 mg, buprenorphine 0.15 mg, 및 0.3 mg을 경막외로 각각 투여하여 혈압과 맥박의 변화, 작용발현기간, 작용 지속 시간, 부작용의 발생을 관찰하여 다음과 같은 결과를 얻었다. 1) 모든 군에서 혈압 및 맥박의 유의한 변동은 초래하지 않았다. 2) 작용 발현은 morphine 2 mg군에서는 약물 주입후 30분에, 나머지 군에서는 15분에 유의하게 나타났다. 3) 진통 지속 시간은 morphine 2 mg 군에서는 $10.79{\pm}3.64$시간이었고, morphine 4 mg군에서는 $21.13{\pm}4.36$시간, buprenorphine 0.15 mg군에서는 $15.19{\pm}3.12$시간, buprenorphine 0.3 mg군에서는 $33.94{\pm}3.97$시간이었다. 4) 부작용의 발생은 buprenorphine군에서 오심, 구토가 많았으며, 졸림증이 현저하게 많았고, 소양감과 배뇨 곤란은 morphine군에서 많았다. 이상의 결과로 수술후의 통증관리에 있어서 경막외로의 buprenorphine주입은 유용한 방법이며, 경막 외 morphine에 비해 장점과 단점을 아울러 포함하고 있다고 사료된다.

• 약학회지
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• 제43권1호
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• pp.55-60
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• 1999

To investigate analgesic mechanism of capsaicin and its analogues (capaicinoids) adenosine release was measured by high performance liquid chromatography from rat spinal cord synaptosomes. Exposure of synaptosomes to $K^+$ and morphine produced a dose dependent release of adenosine in the presence of $Ca^{++}$. Capsaicin (0.1, 1, $10{\;}{\mu}M$), and its analogues: NE-19550 (1, 10, $100{\;}{\mu}M$), DMNE (1, 10, $100{\;}{\mu}M$) and KR 25018 (0.1, 1, $10{\;}{\mu}M$) produced a concentration dependent release of adenosine in the presence of $Ca^{++}$. Nifedifine, L-type voltage sensitive calcium channel blocker, inhibited $K^+$ (6, 12 mM)-and morphine ($10{\;}{\mu}M$)-evoked release of adenosine partially. Capsazepine, a novel capsaicin selective antagonist, blocked only capsaicin and capsaicinoids induced release of adenoside. Therefore, it is suggested that the adenosine release by capsaicin and capsaicinoids having antinociceptive effects involves actvation of capsaicin specific receptor and capsaicin sensitive $Ca^{++}$. channel.