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Interactions between sensory and emotions for chronic pain

Research Project

Project/Area Number 17H05074
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Pain science
Research InstitutionHyogo Medical University

Principal Investigator

KOGA KOHEI  兵庫医科大学, 医学部, 講師 (50768455)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥24,700,000 (Direct Cost: ¥19,000,000、Indirect Cost: ¥5,700,000)
Fiscal Year 2019: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Fiscal Year 2017: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000)
Keywords前帯状回 / 慢性疼痛 / シナプス可塑性 / 神経回路 / 痛み
Outline of Final Research Achievements

Chronic pain consists of sensory and emotional aspects, and both two aspects interact each other. However, the neural mechanisms and circuits on sensory-emotional interactions are still unknown. We focused on the anterior cingulate cortex (ACC), which is involved in chronic pain and anxiety, and studied the selective projections to form presynaptic long-term potentiation in the ACC. We found that the ACC receives inputs from thalamus mono-synaptically as well as poly-synaptically. Furthermore, an animal model of chronic pain attenuated GABAergic inhibitory synaptic transmission in the ACC. An electrophysilogical study showed that a chronic pain model reduced the release of GABA. When we activate muscarinic M1 receptors within the ACC, mechanical hypersensitivity was alleviated through facilitating muscarinic M1 receptors on GABAergic transmissions in the ACC.

Academic Significance and Societal Importance of the Research Achievements

前帯状回皮質は、慢性疼痛と不安の形成に関わる大脳皮質の一つである。前帯状回における興奮性シナプスおよび抑制性シナプスが慢性疼痛によっていかに可塑的変化を形成するかや皮質内の局所神経回路が明らかになると、前帯状回における慢性疼痛や不安の仕組みが解明される。本研究結果は、上位中枢に作用する慢性疼痛に対する創薬開発に役立つ可能性がある。さらに、このような感覚がいかに情動や感情を形成し、相互に作用し合うかの神経分子機構が明らかとなると、様々な感覚ー情動系の解明に発展する広範囲な神経科学分野に貢献できる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (22 results)

All 2019 2018 2017

All Journal Article (15 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 15 results,  Open Access: 13 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Muscarinic M<sub>1</sub> receptors stimulated by intracerebroventricular administration of McN-A-343 reduces the nerve injury-induced mechanical hypersensitivity via GABA<sub>B</sub> receptors rather than GABA<sub>A</sub> receptors in mice2019

    • Author(s)
      Migita K, Nishimura A, Eto F, Koga K, Matsumoto T, Terada K, Hara S, Honda K.
    • Journal Title

      J Pharmacol Sci.

      Volume: 142 Issue: 2 Pages: 50

    • DOI

      10.1016/j.jphs.2019.06.010

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lipopolysaccharide induces mouse translocator protein (18 kDa) expression via the AP-1 complex in the microglial cell line, BV-22019

    • Author(s)
      Shimoyama Shuji、Furukawa Tomonori、Ogata Yoshiki、Nikaido Yoshikazu、Koga Kohei、Sakamoto Yui、Ueno Shinya、Nakamura Kazuhiko
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 9 Pages: 1-15

    • DOI

      10.1371/journal.pone.0222861

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chronic pain models amplify transient receptor potential vanilloid 1 (TRPV1) receptor responses in adult rat spinal dorsal horn2019

    • Author(s)
      Uta Daisuke、Yoshimura Megumu、Koga Kohei
    • Journal Title

      Neuropharmacology

      Volume: 160 Pages: 107753-107753

    • DOI

      10.1016/j.neuropharm.2019.107753

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Animal models of chronic pain increase spontaneous glutamatergic transmission in adult rat spinal dorsal horn in?vitro and in?vivo2019

    • Author(s)
      Uta Daisuke、Kato Go、Doi Atsushi、Andoh Tsugunobu、Kume Toshiaki、Yoshimura Megumu、Koga Kohei
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 512 Issue: 2 Pages: 352-359

    • DOI

      10.1016/j.bbrc.2019.03.051

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stimulating muscarinic M<sub>1</sub> receptors in the anterior cingulate cortex reduces mechanical hypersensitivity via GABAergic transmission in nerve injury rats2019

    • Author(s)
      Koga K, Matsuzaki Y, Migita K, Shimoyama S, Eto F, Nakagawa T, Matsumoto T, Terada K, Mishima K, Furue H, Honda K
    • Journal Title

      Brain Res

      Volume: 1704 Pages: 187

    • DOI

      10.1016/j.brainres.2018.10.013

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ethanol-induced enhancement of inhibitory synaptic transmission in the rat spinal substantia gelatinosa2018

    • Author(s)
      Yamada Akihiro、Koga Kohei、Kume Kazuhiko、Ohsawa Masahiro、Furue Hidemasa
    • Journal Title

      Molecular Pain

      Volume: 14 Pages: 1-13

    • DOI

      10.1177/1744806918817969

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reduced synaptic function of Kainate receptors in the insular cortex of Fmr1 Knock-out mice2018

    • Author(s)
      Qiu Shuang、Wu Yu、Lv Xinyou、Li Xia、Zhuo Min、Koga Kohei
    • Journal Title

      Molecular Brain

      Volume: 11(1):54 Issue: 1 Pages: 1-11

    • DOI

      10.1186/s13041-018-0396-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] GABAB receptor in the antihypersensitive effect in anterior cingulate cortex of partial sciatic nerve ligation model2018

    • Author(s)
      Migita K, Matsuzaki Y, Koga K, Matsumoto T, Mishima K, Hara S, Honda K
    • Journal Title

      J Pharmacological Sciences

      Volume: 137 Issue: 2 Pages: 233-236

    • DOI

      10.1016/j.jphs.2018.05.009

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chronic inflammatory pain induced GABAergic synaptic plasticity in the adult mouse anterior cingulate cortex2018

    • Author(s)
      Koga Kohei、Shimoyama Shuji、Yamada Akihiro、Furukawa Tomonori、Nikaido Yoshikazu、Furue Hidemasa、Nakamura Kazuhiko、Ueno Shinya
    • Journal Title

      Molecular Pain

      Volume: 14 Pages: 1-14

    • DOI

      10.1177/1744806918783478

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Top-down descending facilitation of spinal sensory excitatory transmission from the anterior cingulate cortex2018

    • Author(s)
      Chen Tao、Taniguchi Wataru、Chen Qi-Yu、Tozaki-Saitoh Hidetoshi、Song Qian、Liu Ren-Hao、Koga Kohei、Matsuda Tsuyoshi、Kaito-Sugimura Yae、Wang Jian、Li Zhi-Hua、Lu Ya-Cheng、Inoue Kazuhide、Tsuda Makoto、Li Yun-Qing、Nakatsuka Terumasa、Zhuo Min
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 1-17

    • DOI

      10.1038/s41467-018-04309-2

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] SCRAPPER Selectively Contributes to Spontaneous Release and Presynaptic Long-Term Potentiation in the Anterior Cingulate Cortex2017

    • Author(s)
      Koga Kohei、Yao Ikuko、Setou Mitsutoshi、Zhuo Min
    • Journal Title

      The Journal of Neuroscience

      Volume: 37 Issue: 14 Pages: 3887-3895

    • DOI

      10.1523/jneurosci.0023-16.2017

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Activations of muscarinic M1 receptors in the anterior cingulate cortex contribute to the antinociceptive effect via GABAergic transmission2017

    • Author(s)
      Kohei Koga, Yu Matsuzaki, Kenji Honda, Fumihiro Eto, Tomonori Furukawa, Keisuke Migita, Keiichi Irie, Kenichi Mishima and Shinya Ueno
    • Journal Title

      Molecular Pain

      Volume: 13 Pages: 1-11

    • DOI

      10.1177/1744806917692330

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Propofol anesthesia is reduced in Phospholipase C-related inactive protein type-1 knockout mice2017

    • Author(s)
      Nikaido Y, Furukawa T, Shimoyama S, Yamada J, Migita K, Koga K, Kushikata T, Hirota K, Kanematsu T, Hirata M, Ueno S
    • Journal Title

      The Journal of pharmacology and experimental therapeutics

      Volume: 361(3) Issue: 3 Pages: 367-374

    • DOI

      10.1124/jpet.116.239145

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chronic diazepam administration increases the expression of Lcn2 in the CNS2017

    • Author(s)
      Tomonori Furukawa, Shuji Shimoyama, Yasuo Miki, Yoshikazu Nikaido, Kohei Koga, Kazuhiko Nakamura, Koichi Wakabayashi & Shinya Ueno
    • Journal Title

      Pharmacology Research & Perspectives

      Volume: 5(1) Issue: 1 Pages: 1-12

    • DOI

      10.1002/prp2.283

    • NAID

      120006576912

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuronal and microglial mechanisms for neuropathic pain in the spinal dorsal horn and anterior cingulate cortex.2017

    • Author(s)
      Tsuda M, Koga K, Chen T, Zhuo M.
    • Journal Title

      J Neurochem.

      Volume: 141(4) Issue: 4 Pages: 486-498

    • DOI

      10.1111/jnc.14001

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Chronic pain model alters GABAergic synaptic transmission in the mice anterior cingulate cortex.2019

    • Author(s)
      Koga K, Shimoyama S, Yamada A, Furue H, Nakamura K, Ueno S.
    • Organizer
      The 9th FAOPS
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effects of ethanol on nociceptive synaptic transmission in the rat spinal dorsal horn.2019

    • Author(s)
      Yamada A, Koga K, Kume K, Ohsawa M, Imoto K, Furue H
    • Organizer
      The 9th FAOPS
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Establishment of in vivo field excitatory post synaptic potential (fEPSP) recording system at hippocampal CA3-CA3 synapses.2018

    • Author(s)
      Oishi N, Koga K, Nomoto M, Ohkawa N, Tsujimura S, Sano Y, Saitoh Y, Nishizono H, Matsuo M, Muramatsu S, Inokuchi K
    • Organizer
      第41回 日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Functional roles of presynaptic long-term potentiation in the anterior cingulate cortex for pain and anxiety.2018

    • Author(s)
      Koga K
    • Organizer
      第40回 日本疼痛学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 前帯状回のシナプス前終末における長期増強の形成と不安様行動2018

    • Author(s)
      古賀浩平
    • Organizer
      第27回 神経行動薬理若手研究者の集い
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] The ubiquitin proteasome system regulates presynaptic long-term potentiation in the anterior cingulate cortex2017

    • Author(s)
      Koga K, Yao I, Setou M, Furue H, Zhuo M
    • Organizer
      第95回 日本生理学会大会(高松)
    • Related Report
      2017 Annual Research Report
  • [Presentation] SCRAPPER regulates spontaneous release and presynaptic long-term potentiation in the anterior cingulate cortex2017

    • Author(s)
      Kohei Koga, Ikuko Yao, Mitsutoshi Setou, Hidemasa Furue, Min Zhuo
    • Organizer
      第40回 日本神経科学会年会(千葉)
    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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