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Studies on effects of serotonin in neuron-glia interaction for opioid-induced hyperalgesia.

Research Project

Project/Area Number 18K16475
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 55050:Anesthesiology-related
Research InstitutionNiigata University

Principal Investigator

SASAKI MIKA  新潟大学, 医歯学系, 助教 (20774061)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsセロトニン / アストロサイト / モルヒネ / オピオイド誘発性痛覚過敏 / 脊髄後角
Outline of Final Research Achievements

In this study, a model of opioid-induced hyperalgesia (OIH) with repeated intraperitoneal administration of morphine was developed to elucidate the pathogenesis of paradoxical opioid-induced hyperalgesia, and the involvement of serotonin was investigated. Morphine-induced OIH was inhibited by the 5-HT3 receptor antagonist ondansetron (OND) and the serotonin synthesis inhibitor para-chlorophenylalanine (PCPA). On the other hand, there was an increase in pain-related protein phosphorylated ERK and astrocyte activation during the onset of OIH, but no inhibitory effect of OND or PCPA administration.
These results suggest that serotonin in the dorsal horn of the spinal cord is largely involved in OIH and that astrocyte activation may be secondary.

Academic Significance and Societal Importance of the Research Achievements

麻薬性鎮痛薬(オピオイド)は,周術期疼痛管理やがん性疼痛の緩和治療に必須の鎮痛薬である一方,オピオイドの比較的大量投与や長期使用により,鎮痛効果とは逆の作用である逆説的な痛覚過敏(Opioid-Induced Hyperalgesia : OIH)を生じることが知られており,オピオイドの使用に対する臨床上の解決すべき問題となっている.本研究から,OIHにはセロトニンが深く関与していることが明らかになり,セロトニン及びその受容体がOHIの治療・予防標的となりうることが示された.

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (3 results)

All 2019

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Acute spatial spread of NO-mediated potentiation during hindpaw ischaemia in mice.2019

    • Author(s)
      Onishi T, Watanabe T, Sasaki M, Kamiya Y, Horie M, Tsukano H, Hishida R, Kohno T, Takebayashi H, Baba H, Shibuki K
    • Journal Title

      J Physiol.

      Volume: 597 Issue: 13 Pages: 3441-3455

    • DOI

      10.1113/jp277615

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neurosteroid dehydroepiandrosterone sulphate enhances pain transmission in rat spinal dorsal horn2019

    • Author(s)
      Yamamoto Goh、Kamiya Yoshinori、Sasaki Mika、Ikoma Miho、Baba Hiroshi、Kohno Tatsuro
    • Journal Title

      British Journal of Anaesthesia

      Volume: 印刷中 Issue: 2 Pages: e215-e225

    • DOI

      10.1016/j.bja.2019.03.026

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Opioid-induced hyperalgesia by chronic administration of morphine is caused by serotonin in spinal dorsal horn and, in part, through the 5-HT3 receptor.2019

    • Author(s)
      Mika Sasaki., Yoshinori Kamiya., Keiko Bamba., Moegi Tanaka. and Takeshi Ohnishi.
    • Organizer
      Society for Neuroscience 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2021-02-19  

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