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Development of animal models for postoperative pain that mimic clinical pathophysiological pain states

Research Project

Project/Area Number 19H03750
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 55050:Anesthesiology-related
Research InstitutionShinshu University

Principal Investigator

Kawamata Mikito  信州大学, 学術研究院医学系, 教授 (90315523)

Co-Investigator(Kenkyū-buntansha) 田中 聡  信州大学, 学術研究院医学系, 准教授 (60293510)
石田 高志  信州大学, 学術研究院医学系(医学部附属病院), 講師 (60531952)
石田 公美子 (松尾公美子)  信州大学, 学術研究院医学系, 助教 (80467191)
杉山 由紀  信州大学, 学術研究院医学系(医学部附属病院), 講師 (10468100)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2021: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Keywords術後痛 / 外科的侵襲 / 慢性化 / 炎症細胞 / 神経新生 / 術後痛モデル / 炎症 / 血管新生 / 神経申請 / マイクログリア / 動物モデル / 四肢手術モデル / 開腹手術モデル / メカニズム / 病巣 / 遷延性術後痛 / 炎症性疼痛 / 慢性術後痛 / 新規動物モデル
Outline of Research at the Start

新規術後鎮痛法の開発のためには、病変部位への外科侵襲による、臨床をより反映した新たな術後痛モデルの開発を行い、これを元にしたトランスレーショナルリサーチが不可欠である。本研究では炎症性病変を導入後、炎症性疼痛が消退した病変部位への外科的切開を加えた(I) 四肢手術後痛モデルと(II) 開腹手術後痛モデルを新たに開発し、行動生理学的、免疫組織化学的、薬理学的機序解明をもとに、新規術後鎮痛薬・法の開発を行う。

Outline of Final Research Achievements

Although the plantar incision-induced pain model of the rat has been used as a model of postoperative pain in humans, surgical injury of normal tissues is likely a model of trauma-induced pain to a healthy limb. The postoperative pain actually encountered in clinical practice is caused by surgical injury to the site where not only the skin but also other deep tissues and/or organs are damaged by surgery, or where chronic inflammation, angiogenesis, or neurogenesis has occurred due to the underlying disease has occurred. Therefore, it is necessary to develop a postoperative pain model that mimics actual surgery and lesions. We developed a rat plantar incision model with deep muscle injury and an incision model chronic inflammation of the plantar foot, and elucidated the mechanism of prolonged postoperative pain.

Academic Significance and Societal Importance of the Research Achievements

動物モデルでの術後痛は炎症物質の投与による炎症痛と同じ機序と考えられてきた。しかし炎症痛モデルの結果を元に、術後鎮痛薬・法を行なっても有用性を示さないことが散見された。そこでBrennanらがラット足底切開モデルを術後痛モデルとして発表し、このモデルが臨床上の術後痛をより反映することが示された。しかし、このモデルでは慢性術後痛を呈する動物はなく、亜急性期や慢性期の術後鎮痛のためには、より臨床を反映した動物モデルが求められている。われわれの今回開発した動物モデルは、長期間の遷延する術後痛を呈し、特に自発痛も長く続き、より臨床を反省しており、これらのモデルを用いて新たな治療が生まれる可能性がある。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (29 results)

All 2021 2020 2019

All Journal Article (16 results) (of which Peer Reviewed: 16 results,  Open Access: 12 results) Presentation (8 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Book (5 results)

  • [Journal Article] Plantar incision with severe muscle injury can be a cause of long-lasting postsurgical pain in the skin.2021

    • Author(s)
      Yoshiyama Y, Sugiyama Y, Ishida K, Fuseya S, Tanaka S, Kawamata M
    • Journal Title

      Life Sciences

      Volume: 275 Pages: 119389-119389

    • DOI

      10.1016/j.lfs.2021.119389

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] he histamine H1 receptor antagonist hydroxyzine enhances sevoflurane and propofol anesthesia: A quantitative EEG study.2021

    • Author(s)
      Tanaka R, Tanaka S, Hayashi K, Iida K, Sawa T, Kawamata M
    • Journal Title

      Clinical Neurophysiology

      Volume: 132 Issue: 9 Pages: 2054-2061

    • DOI

      10.1016/j.clinph.2021.05.024

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] nother route of CO2 gas excretion independent of red blood cells in human lungs2021

    • Author(s)
      Ide S, Arai N, Morimitsu N, Momose H, Hayashi M, Watanabe AT, Ishida T, Tanaka S, Seto T, Kawai Y, Kawamata M, Ohhashi T:
    • Journal Title

      European Journal of Physiology

      Volume: 473 Issue: 10 Pages: 1657-1666

    • DOI

      10.1007/s00424-021-02586-3

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Successful management of a patient with intraoperative bleeding of more than 80,000 mL and usefulness of QTc monitoring for calcium correction.2021

    • Author(s)
      Sugiyama Y, Aiba K, Arai N, Ito M, Urasawa M, Hirose C, Murakami I, Tanaka R, Yamada T, Iida K, Nakamura H, Kawamata M
    • Journal Title

      Case reports in Anesthesiology

      Volume: 2021 Pages: 6635696-6635696

    • DOI

      10.1155/2021/6635696

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Catheter-induced anaphylaxis and determination of the causative catheter in a patient undergoing neuroendovascular surgery: a case report2021

    • Author(s)
      Sugiyama Y, Kaori Numata, Watanabe N, Murakami T, Urasawa M, Murakami I, Koyama J, Kawamata M
    • Journal Title

      JA Clin Rep

      Volume: 7 Issue: 1 Pages: 59-59

    • DOI

      10.1186/s40981-021-00463-7

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ifferential effects of sevoflurane and propofol on an electroretinogram and visual evoked potentials2020

    • Author(s)
      Tanaka R, Tanaka S, Ichino T, Ishida T, Fuseya S, Kawamata M
    • Journal Title

      Journal of Anesthesia

      Volume: 34 Issue: 2 Pages: 298-302

    • DOI

      10.1007/s00540-020-02733-7

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acute postoperative pain is correlated with the early onset of postpartum depression after cesarean section: a retrospective cohort study2020

    • Author(s)
      Shen D, Hasegawa-Moriyama M, Ishida K, Fuseya S, Tanaka S, Kawamata M
    • Journal Title

      Journal of Anesthesia

      Volume: 34 Issue: 4 Pages: 607-612

    • DOI

      10.1007/s00540-020-02789-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of an aerosol box on tracheal intubation difficulty.2020

    • Author(s)
      Wakabayashi R, Ishida T, Yamada T. Kawamata M:
    • Journal Title

      Journal of Anesthesia

      Volume: 34 Issue: 5 Pages: 790-793

    • DOI

      10.1007/s00540-020-02835-2

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phospholipase Cβ3 Expressed in Mouse DRGs is Involved in Inflammatory and Postoperative Pain2020

    • Author(s)
      Ide Susumu、Kawamata Tomoyuki、Ishida Kumiko、Fuseya Satoshi、Ishida Takashi、Sugiyama Yuki、Kawamata Mikito、Tanaka Satoshi
    • Journal Title

      Journal of Pain Research

      Volume: Volume 13 Pages: 3371-3384

    • DOI

      10.2147/jpr.s280565

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anesthetic management of a patient with musculocontractural Ehlers-Danlos syndrome undergoing scoliosis surgery2020

    • Author(s)
      Wakabayashi R, Tanaka S, Tsuchiyama K, Yamamoto K, Maruyama Y, Numata K, Kawamata M
    • Journal Title

      JA Clin Rep

      Volume: 6 Issue: 1 Pages: 46-46

    • DOI

      10.1186/s40981-020-00352-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficacy and safety of controlled-release oxycodone for the management of moderate-to severe chronic low back pain in Japan: results of an enriched enrollment randomized withdrawal study followed by an open-label extension study.2019

    • Author(s)
      Kawamata M, Iseki M, Kawakami M, Yabuki S, Sasaki T, Ishida M, Nishiyori A, Hida H, Kikuchi S
    • Journal Title

      J Pain Research.

      Volume: 12 Pages: 363375-363375

    • DOI

      10.2147/jpr.s179110

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcranial motor-evoked potentials of laryngeal muscles for intraoperative neuromonitoring of the vagus nerve during thyroid surgery2019

    • Author(s)
      Ichino Takashi、Tanaka Satoshi、Tanaka Ryusuke、Tanaka Naruaki、Ishida Takashi、Sugiyama Yuki、Kawamata Mikito
    • Journal Title

      Journal of Anesthesia

      Volume: 33 Issue: 2 Pages: 221-229

    • DOI

      10.1007/s00540-018-2601-x

    • NAID

      40021867626

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endogenous Calcitonin Gene-Related Peptide Deficiency Exacerbates Postoperative Lymphedema by Suppressing Lymphatic Capillary Formation and M2 Macrophage Accumulation.2019

    • Author(s)
      Matsui S, Tanaka M, Kamiyoshi A, Sakurai T, Ichikawa-Shindo Y, Kawate H, Dai K, Cui N, Wei Y, Tanaka M, Kakihara S, Nakamura K, Yamauchi A, Ishida K, Tanaka S, Kawamata M, Shindo T
    • Journal Title

      Am J Pathol.

      Volume: 189 Pages: 24872502-24872502

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy And Safety Of Controlled-Release Oxycodone For The Management Of Moderate-To-Severe Chronic Non-Cancer Pain In Japanese Patients: Results From An Open-Label Study.2019

    • Author(s)
      Kawamata M, Iseki M, Kawakami M, Yabuki S, Sasaki T, Ishida M, Nishiyori A, Hida H, Kikuchi S
    • Journal Title

      J Pain Research.

      Volume: 12 Pages: 34233436-34233436

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Severe mitral regurgitation due to geometric changes in the mitral valve after surgical aortic valve replacement.2019

    • Author(s)
      Wakabayashi R, Ide S, Ishida T, Tanaka S, Kawamata M
    • Journal Title

      JA Clin Rep

      Volume: 5 Issue: 1 Pages: 59-59

    • DOI

      10.1186/s40981-019-0277-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reply to the letter to the editor.2019

    • Author(s)
      Tanaka S, Ichino T, Kawamata M
    • Journal Title

      J Anesth.

      Volume: 33 Issue: 2 Pages: 349-349

    • DOI

      10.1007/s00540-019-02617-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] 麻酔科医が知っておくべき術後痛の基礎と臨床2021

    • Author(s)
      川真田 樹人
    • Organizer
      日本ペインクリニック学会第55回学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 周術期の痛みを考える 「帝王切開による術後痛を診る」2021

    • Author(s)
      川真田 樹人
    • Organizer
      第125回日本産科麻酔学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Early Complications And Risk Factors Related To Cerebrospinal Fluid Drainage In Thoracic Aortic Aneurism Surgery.2020

    • Author(s)
      Aiba K, Sugiyama Y, Shimao T, Kawamata M.
    • Organizer
      Annual Meeting of American Society of Anesthesiologists
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Insertion of different types of supraglottic airway devices causes different deformity of the larynx during medialization laryngoplasty: a report of two cases2020

    • Author(s)
      Maruyama Y, Sugiyama Y, Numata K, Kawamata M
    • Organizer
      Euroanaesthesia
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 術後痛管理-その実際と最新の知見-:高齢患者の術後痛管理の実際2020

    • Author(s)
      川真田 樹人
    • Organizer
      日本臨床麻酔学会第40回大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 遷延性術後痛発生のメカニズム解明と予防への発展] 遷延性術後痛予防における、術後鎮痛の重要性と課題.2020

    • Author(s)
      田中 聡, 川真田 樹人
    • Organizer
      第42回日本疼痛学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] New insights into the descending inhibitory pain system.2019

    • Author(s)
      Kawamata M
    • Organizer
      The 27th Annual Meeting of the Chinese Society of Anesthesiology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 産科麻酔における痛み:母体と胎児の痛み研究.2019

    • Author(s)
      川真田 樹人
    • Organizer
      第123回日本産科麻酔学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Book] 緊急時の全身麻酔. 救急・集中治療 ICU治療指針Ⅲ2020

    • Author(s)
      杉山 由紀, 川真田 樹人
    • Publisher
      総合医学社
    • ISBN
      4883785645
    • Related Report
      2020 Annual Research Report
  • [Book] 急性疼痛の病態. 疼痛医学2020

    • Author(s)
      川真田 樹人, 石田 公美子, 田中 聡
    • Publisher
      医学書院
    • ISBN
      9784260040839
    • Related Report
      2020 Annual Research Report
  • [Book] 麻酔科学レビュー 20202020

    • Author(s)
      川真田 樹人
    • Publisher
      総合医学社
    • ISBN
      9784883786961
    • Related Report
      2020 Annual Research Report
  • [Book] 術後痛管理. 新戦略に基づく麻酔・周術期医学 麻酔科医のための周術期の診療ガイドライン活用術.2020

    • Author(s)
      石田 高志, 川真田 樹人
    • Publisher
      中山書店
    • ISBN
      9784521743288
    • Related Report
      2020 Annual Research Report
  • [Book] 麻酔科学レビュー 20192019

    • Author(s)
      川真田 樹人
    • Total Pages
      5
    • Publisher
      総合医学社
    • Related Report
      2019 Annual Research Report

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Published: 2019-04-18   Modified: 2023-01-30  

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