• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Molecular mechanism of chronic pain with its onset in the limbic system and development of new therapeutic agents

Research Project

Project/Area Number 20K21654
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research InstitutionOsaka University

Principal Investigator

Shimada Shoichi  大阪大学, 医学系研究科, 教授 (20216063)

Co-Investigator(Kenkyū-buntansha) 中村 雪子  大阪大学, 医学系研究科, 特任講師 (90548083)
近藤 誠  大阪市立大学, 大学院医学研究科, 教授 (50633012)
小山 佳久  大阪大学, 医学系研究科, 助教 (40397667)
臼井 紀好  大阪大学, 医学系研究科, 准教授 (00784076)
Project Period (FY) 2020-07-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2021: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords慢性疼痛 / 条件付け / 大脳辺縁系 / オピオイド / 情動
Outline of Research at the Start

繰り返す痛みの経験が条件づけとなり悪化する慢性疼痛がある。この様な疼痛では、元々の疼痛の原因である組織損傷や炎症が治った後でも、痛みが継続し、改善しない場合がある。痛みに関するこの様な条件づけが脳内で形成されると、それが慢性疼痛などの長期にわたる難治性疼痛の原因の1つになると考えられ、その適切な治療法も見つかっていない。我々はこの現象に着目し、痛みの原因が除去された後でも条件づけによって痛みが継続するモデルマウスの開発に成功した。本研究では、条件づけによって増強する疼痛に関わる神経回路とそのメカニズムを明らかにすると共に、条件づけによって生じる難治性の痛みの治療薬を新しく開発することにある。

Outline of Final Research Achievements

To analyze the mechanism of chronic pain that persists after tissue damage has healed, we have developed a mouse model of conditioning-induced pain. The pain response elicited by this conditioning was reduced by fentanyl but not by ibuprofen, pregabalin, or fluvoxamine, which resembles the pharmacological characteristics of analgesics effective for chronic pain. We have observed c-fos expression and found that neither peripheral nervous system nor the dorsal horn of the spinal cord was involved, but rather several limbic areas in the brain are associated with this conditioning-induced pain. We have also examined various compounds and have found a compound that exhibited analgesic effects equivalent to opioids for pain caused by this conditioning.

Academic Significance and Societal Importance of the Research Achievements

慢性疼痛は難治性の疾患で、唯一オピオイドのフェンタニルが高い治療効果を示す。特に米国では慢性疼痛の治療目的で、鎮痛薬として処方されたオピオイドがきっかけとなり薬物依存者が急増し、乱用による過剰摂取が原因となる死亡者数が年間の交通事故死亡者数5万人を大幅に超え、大きな社会的問題となっている。本研究では、オピオイドに替わる依存性のない慢性疼痛治療薬の開発を目指す。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (9 results)

All 2022 2021 2020

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 7 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Length impairments of the axon initial segment in rodent models of attention-deficit hyperactivity disorder and autism spectrum disorder2022

    • Author(s)
      Noriyoshi Usui, Xiaoye Tiane, Wakana Harigai, Shogo Togawa, Ryo Utsunomiya, Tomomi Doi, Ko Miyoshi, Koh Shinoda, Junya Tanaka, Shoichi Shimada, Taiichi Katayama, Takeshi Yoshimura
    • Journal Title

      Neurochemistry International

      Volume: 153 Pages: 105273-105273

    • DOI

      10.1016/j.neuint.2021.105273

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Early life stress alters gene expression and cytoarchitecture in the prefrontal cortex leading to social impairment and increased anxiety.2021

    • Author(s)
      Usui N, Ono Y, Aramaki R, Berto S, Konopka G, Matsuzaki H, Shimada S.
    • Journal Title

      Frontiers in Genetics

      Volume: 12 Pages: 754198-754198

    • DOI

      10.3389/fgene.2021.754198

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Characterization of Early Life Stress-Affected Gut Microbiota.2021

    • Author(s)
      Usui N, Matsuzaki H, Shimada S.
    • Journal Title

      Brain Sci.

      Volume: 11(7) Issue: 7 Pages: 913-913

    • DOI

      10.3390/brainsci11070913

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a new method for assessing otolith function in mice using three-dimensional binocular analysis of the otolith-ocular reflex.2021

    • Author(s)
      Harada S, Imai T, Takimoto Y, Ohta Y, Sato T, Kamakura T, Takeda N, Kitahara T, Kondo M, Ueno Y, Shimada S, Inohara H.
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 17191-17191

    • DOI

      10.1038/s41598-021-96596-x

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Zbtb16 regulates social cognitive behaviors and neocortical development.2021

    • Author(s)
      Usui N, Berto S, Konishi A, Kondo M, Konopka G, Matsuzaki H, Shimada S.
    • Journal Title

      Translational Psychiatry

      Volume: 11 Issue: 1 Pages: 242-242

    • DOI

      10.1038/s41398-021-01358-y

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cochlear protection against noise exposure requires serotonin type 3A receptor via the medial olivocochlear system.2021

    • Author(s)
      Ohata K, Kondo M, Ozono Y, Hanada Y, Sato T, Inohara H, Shimada S.
    • Journal Title

      The FASEB Journal

      Volume: 35 Issue: 5

    • DOI

      10.1096/fj.202002383r

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pain-like behavior in mice can be induced by the environmental context in which the pain stimulus was previously given.2021

    • Author(s)
      Nakamura Y, Okano Y, Sato M, Kobayashi M, Yamaguchi T, Sumi T, Koyama Y, Kondo M, Usui N, Shimada S.
    • Journal Title

      NeuroReport

      Volume: 32 Issue: 5 Pages: 386-393

    • DOI

      10.1097/wnr.0000000000001607

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bladder urothelium converts bacterial lipopolysaccharide information into neural signaling via an ATP-mediated pathway to enhance the micturition reflex for rapid defense.2020

    • Author(s)
      Ueda N, Kondo M, Takezawa K, Kiuchi H, Sekii Y, Inagaki Y, Soda T, Fukuhara S, Fujita K, Uemura M, Imamura R, Miyagawa Y, Nonomura N, Shimada S.
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 21167-21167

    • DOI

      10.1038/s41598-020-78398-9

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Patent(Industrial Property Rights)] セロトニン3受容体アゴニストによる疼痛の治療2020

    • Inventor(s)
      島田昌一、中村雪子、近藤誠
    • Industrial Property Rights Holder
      島田昌一、中村雪子、近藤誠
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report
    • Overseas

URL: 

Published: 2020-08-03   Modified: 2024-12-25  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi