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Development of novel Nav1.7 antagonist by using molecular pharmacological methods

Research Project

Project/Area Number 18K08852
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55050:Anesthesiology-related
Research InstitutionShinshu University

Principal Investigator

Ishida Takashi  信州大学, 学術研究院医学系(医学部附属病院), 講師 (60531952)

Co-Investigator(Kenkyū-buntansha) 清澤 研吉  信州大学, 医学部附属病院, 助教(特定雇用) (50624772)
木村 忠史  国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (60344214)
中田 勉  信州大学, 学術研究院総合人間科学系, 准教授 (70452141)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords痛み / 局所麻酔薬 / ナトリウムチャネル
Outline of Final Research Achievements

Congenital insensitivity to pain is a rare autosomal-recessive disorder. Congenital insensitivity to pain is caused by mutations in the gene encoding for the Nav1.7 channel. We analyzed the DNA from the patient who had no pain perception and a novel mutation in SCA9A was detected. The mutation of SCA9A encoded the pore of Nav1.7 channel. We investigated the mutated Nav1.7 function by electrophysiological method. The result suggests decreased ramp current might contribute to insensitivity to pain. We also created the point mutation knock in mice and investigated the behavior to nociceptive stimuli and the channel function of mutated Nav1.7 at dorsal root ganglion. The knock in mice had reduced pain perception to heat and mechanical stimuli and the amplitude of the current produced by mutated Nav1.7 was decreased.

Academic Significance and Societal Importance of the Research Achievements

痛みは体の異常や危険を察知するために重要な感覚であるが、手術や疾患による過剰な痛みは不快感を与えるだけでなく日常生活に支障をきたすこともある。今回、新しい鎮痛薬のターゲットを見つけるにあたって無痛症患者が痛みを感じない機序を調べた。無痛症患者では電位依存性ナトリウムチャネル(Nav1.7)の機能が低下していることが明らかとなり、このNav1.7をターゲットとすれば安全かつ効果的な鎮痛薬の開発が行える可能性があることが示された。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (8 results)

All 2020 2019 2018

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [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] 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] 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 Research-status Report
    • Peer Reviewed
  • [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
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Plasma ropivacaine concentration after TAP block in a patient with cardiac and renal failure2018

    • Author(s)
      Ishida Takashi、Tanaka Satoshi、Sakamoto Akiyuki、Hirabayashi Takanobu、Kawamata Mikito
    • Journal Title

      Local and Regional Anesthesia

      Volume: Volume 11 Pages: 57-60

    • DOI

      10.2147/lra.s173877

    • NAID

      120007113455

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Knockdown of TRPV2 channels in sensory neurons increases limb use and weight bearing but does not affect spontaneous flinching behavior in a mouse model of bone cancer2018

    • Author(s)
      Yamamoto Katsumi、Tanaka Satoshi、Fuseya Satoshi、Ishida Takashi、Zhang Hao、Kawamata Tomoyuki、Kawamata Mikito
    • Journal Title

      Molecular Pain

      Volume: 14 Pages: 1-11

    • DOI

      10.1177/1744806918819942

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Successful anesthetic management during dual stenting of the esophagus and trachea for a tracheo-esophageal fistula: a case report.2019

    • Author(s)
      Nakamura H, Yamamoto K, Wakabayashi R, Murakami I, Ishida T, Kawamata M
    • Organizer
      Euroanaesthesia
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Estimation of Systemic Vascular Resistance by Photoplethysmographic Analysis during General Anaesthesia: A Pilot Study.2019

    • Author(s)
      Takekoshi M, Wakabayashi R, Kodaira T, Tanaka R, Ishida T, Kawamata M
    • Organizer
      Euroanaesthesia
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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