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Clarification of mechanisms underlying the disability of morphine tolerance and dependence in the appropriate medication of morphine in palliative care of cancer pain

Research Project

Project/Area Number 10672152
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionNAGASAKI UNIVERSITY

Principal Investigator

TAKAHASHI Masakatsu  Nagasaki University, Graduate School of Pharmaceutical Sciences, Associate Professor, 大学院・薬学研究科, 助教授 (90112383)

Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Keywordsphasic pain / tonic pain / Analgesic effect / morphine tolerance / formalin test / U-50,488H / cancer pain releaf / emotionality / モルヒネ / 耐性 / 鎮痛 / オピオイド / 依存性 / 慢性疼痛モデル動物 / アンチオピオイド / ストレス / ホルマリンテスト
Research Abstract

In contrast to previous reports that repeated treatment with morphine rapidly develops tolerance to its analgesic effect, recent clinical findings have shown that morphine did not develop tolerance when used for the palliative of cancer pain. To elucidate such discrepancies, development of tolerance to morphine and U-50,488H, μ- and κ-opioid receptor agonists, respectively, given daily subcutaneously (s.c.), intracerebroventricularly (i.c.v.) or intrathecally (i.t.), and, DPDPE, a selective δ-opioid receptor agonist given i.c.v. and i.t., was investigated by both tail-pinch (TP) method for phasic pain and formalin (FL) test for persistent pain stimulation, from the view of differences in pain types between cancer pain and phasic pain stimulation in the test screening for analgesics.
Daily injection of morphine as well as U-50,488H resulted in the gradual loss of analgesic effect, indicating the development of tolerance to the effect in the TP test by any route of administration; however … More , in the FL test, both compounds given s.c. and i.c.v. did not develop tolerance whereas tolerance developed by i.t. administration, supporting above hypothesis that tolerance to analgesic effect of morphine against tonic pain such as cancer pain would be hard to develop. On the other hand, DPDPE given i.c.v. and i.t. easily developed tolerance in both tests. Thus, common mechanisms possibly underlie in the development of tolerance to the suppression of tonic pain by these μ- and κ-opioid receptor agonists, and advantageous clinical use of μ- and κ-agonists but not δ-opioid type is proposed. Additionally, both supraspinal and spinal sites are likely to participate in the development of tolerance to these opioids in the phasic pain, whereas supraspinal site is rather important for the disability of development of tolerance to the suppressive effect of morphine and U-50,488H on the tonic pain stimulation. An anxiolytic drug diazepam also suppressed formalin pain responses. The clinical findings that emotional factors such as anxiety, fear and despair play roles in the production and intensities of chronic pain, are therefore, firstly evidenced by this animal experiment. Less

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Masakatsu Takahashi: "Characterization of socio-psychological stress-induced antinociception in the formalin test in mice"Jpn. J. Pharmacol. 79(1). 83-87 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiroko Furunaga: "Effects of Try-MIF-1 on stress-induced analgesia and the blockade of development of morphine tolerance by stress in mice"Jpn. J. Pharmacol. 79(2). 231-235 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yunden Jinamaa: "Anti-analgesic and anti-amnesic effect of complement C3a"Life Sci. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Masakatsu Takahashi: "Characterization of socio-psychlogical stress-induced antinociception in the formalin test in mice"Jpn. J. Pharmacol.. 79(1). 83-87 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiroko Fukunaga: "Effects of Tyr-MIF-1 on stress-induced analgesia and the blockade of development of morphine tolerance by stress in mice"Jpn. J. Pharmacol.. 79(2). 231-235 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yunden Jinsmaa: "Anti-analgesic and anti-amnesic effect of complement C3a"Life Sci.. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Masakatsu Takahashi: "Characterization of socio-psychologicol stress-induced antinociception in the formalin test in mice"Jpn.J.Pharmacol.. 79(1). 83-87 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hiroko Fukunaga: "Effects of Tyr-MlF-l on stress-induced analgesia and the blockade of development of morphine tolerance tolerance by stress in mice"Jpn.J.Pharmacol. 79(2). 231-235 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Masakatsu Takahashi: "Characterization of Socio-psychological Stress-induced Antinociception in the Formalin Test in Mice" Jpn.J.Pharmacol.79. 83-87 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hiroko Fukunaga: "Effects of Tyr-MIF-1 on Stress-Induced Analgesia and the Blockacle of Development of Morphine Tolerance by Stress in Mice" Jpn.J.Pharmacol.79. 231-235 (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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