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Visualization and quantification of the oxytocinergic pain and inflammation-related descending inhibitory pathways using transgenic rats

Research Project

Project/Area Number 17K11039
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionUniversity of Occupational and Environmental Health, Japan

Principal Investigator

Suzuki Hitoshi  産業医科大学, 医学部, 助教 (80644880)

Co-Investigator(Kenkyū-buntansha) 上田 陽一  産業医科大学, 医学部, 教授 (10232745)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords神経障害性疼痛 / オキシトシン / 視床下部 / 脊髄後角 / 遺伝子改変動物 / 単量体赤色蛍光 / トランスジェニックラット / 坐骨神経部分結紮 / in-situハイブリダイゼーション / CRPSモデル / 難治性疼痛
Outline of Final Research Achievements

We examined the Oxytocinergic system in the hypothalamo-neurohypophysial and hypothalamo-spinal pathway using a rat neuropathic pain model induced by partial sciatic nerve ligation (PSL). In the present study, we used transgenic rats expressing an oxytosin (OXT)-monomeric red fluorescent protein 1 (mRFP1) fusion gene.
In the PSL model, significant increase in the OXT-mRFP1 expression was observed in the posterior pituitary (PP), the supraoptic nucleus (SON), and paraventricular nucleus (PVN). In addition, significant increase of the mRNA levels of OXT and mRFP1 in the SON, and PVN were observed. Furthermore, OXT-mRFP1 granules with positive fluorescent reaction were remarkably increased in laminae I and II of the ipsilateral dorsal horn. These results suggest that neuropathic pain induced by PSL upregulates hypothalamic OXT synthesis and transportation to the OXTergic axon terminals in the PP and spinal cord.

Academic Significance and Societal Importance of the Research Achievements

我々は神経障害性疼痛モデルラットにおけるオキシトシン(OXT)の発現動態を明らかにすることで、神経障害性疼痛によって内因性にOXTニューロンが活性化され疼痛の受容調節に深く関わっている事を明らかにした。今回の研究ではOXTが神経障害性疼痛などの慢性疼痛・難治性疼痛の病態に関与していることを明らかにし、今後治療のターゲットとなり得る示すことが出来た事で学術的にも社会的にも意義のある研究であったと言える。

Report

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

    (33 results)

All 2020 2019 2018 2017

All Journal Article (15 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 14 results,  Open Access: 7 results) Presentation (18 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Acute Mono-Arthritis Activates the Neurohypophysial System and Hypothalamo-Pituitary Adrenal Axis in Rats.2020

    • Author(s)
      Nishimura H, Kawasaki M, Matsuura T, Suzuki H, Motojima Y, Baba K, Ohnishi H, Yamanaka Y, Fujitani T, Yoshimura M, Maruyama T, Ueno H, Sonoda S, Nishimura K, Tanaka K, Sanada K, Onaka T, Ueta Y, Sakai A.
    • Journal Title

      Front Endocrinol (Lausanne)

      Volume: 11 Pages: 43-43

    • DOI

      10.3389/fendo.2020.00043

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuropathic Pain Up-Regulates Hypothalamo-Neurohypophysial and Hypothalamo-Spinal Oxytocinergic Pathways in Oxytocin-Monomeric Red Fluorescent Protein 1 Transgenic Rat2019

    • Author(s)
      Nishimura Haruki、Kawasaki Makoto、Suzuki Hitoshi、Matsuura Takanori、Motojima Yasuhito、Ohnishi Hideo、Yamanaka Yoshiaki、Yoshimura Mitsuhiro、Maruyama Takashi、Saito Reiko、Ueno Hiromichi、Sonoda Satomi、Nishimura Kazuaki、Onaka Tatsushi、Ueta Yoichi、Sakai Akinori
    • Journal Title

      Neuroscience

      Volume: 406 Pages: 50-61

    • DOI

      10.1016/j.neuroscience.2019.02.027

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Is Arthroscopic Hip Labral Repair/Reconstruction Surgery Effective for Treating Femoroacetabular Impingement in the Presence of Osteoarthritis?2019

    • Author(s)
      Nakashima Hirotaka、Utsunomiya Hajime、Kanezaki Shiho、Suzuki Hitoshi、Nakamura Eiichiro、Larson Christopher M.、Sakai Akinori、Uchida Soshi
    • Journal Title

      Clinical Journal of Sport Medicine

      Volume: - Issue: 4 Pages: 1-1

    • DOI

      10.1097/jsm.0000000000000768

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Higher risk of cam regrowth in adolescents undergoing arthroscopic femoroacetabular impingement correction: a retrospective comparison of 33 adolescent and 74 adults.2019

    • Author(s)
      Arashi T, Murata Y, Utsunomiya H, Kanezaki S, Suzuki H, Sakai A, Uchida S
    • Journal Title

      Acta Orthop

      Volume: 90(6) Issue: 6 Pages: 547-553

    • DOI

      10.1080/17453674.2019.1678091

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Patients aged in their 70s do not have a high risk of progressive osteoarthritis following arthroscopic femoroacetabular impingement correction and labral preservation surgery2019

    • Author(s)
      Honda Eisaburo、Utsunomiya Hajime、Hatakeyama Akihisa、Nakashima Hirotaka、Suzuki Hitoshi、Matsuda Dean K.、Sakai Akinori、Uchida Soshi
    • Journal Title

      Knee Surgery, Sports Traumatology, Arthroscopy

      Volume: - Issue: 5 Pages: 1648-1655

    • DOI

      10.1007/s00167-019-05520-4

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Role of Trpv1 and Trpv4 in surgical incision-induced tissue swelling and Fos-like immunoreactivity in the central nervous system of mice2018

    • Author(s)
      Motojima Yasuhito、Nishimura Haruki、Ueno Hiromichi、Sonoda Satomi、Nishimura Kazuaki、Tanaka Kentaro、Saito Reiko、Yoshimura Mitsuhiro、Maruyama Takashi、Matsuura Takanori、Suzuki Hitoshi、Kawasaki Makoto、Ohnishi Hideo、Sakai Akinori、Ueta Yoichi
    • Journal Title

      Neuroscience Letters

      Volume: 678 Pages: 76-82

    • DOI

      10.1016/j.neulet.2018.05.001

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Arthroscopic Management for Acetabular Rim Stress Fracture and Osteochondritis Dissecans in the Athlete With Hip Dysplasia2018

    • Author(s)
      Uchida Soshi、Shimizu Yuki、Yukizawa Yohei、Suzuki Hitoshi、Pascual-Garrido Cecilia、Sakai Akinori
    • Journal Title

      Arthroscopy Techniques

      Volume: 7 Issue: 5 Pages: e533-e539

    • DOI

      10.1016/j.eats.2018.01.007

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Endoscopic Shelf Acetabuloplasty for Treating Acetabular Large Bone Cyst in Patient With Dysplasia2018

    • Author(s)
      Yamada Kazuki、Matsuda Dean K.、Suzuki Hitoshi、Sakai Akinori、Uchida Soshi
    • Journal Title

      Arthroscopy Techniques

      Volume: 7 Issue: 7 Pages: e691-e697

    • DOI

      10.1016/j.eats.2018.03.005

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Arthroscopic treatment for symptomatic lateral discoid meniscus: The effects of different ages, groups and procedures on surgical outcomes2018

    • Author(s)
      Ohnishi Yasuo、Nakashima Hirotaka、Suzuki Hitoshi、Nakamura Eiichiro、Sakai Akinori、Uchida Soshi
    • Journal Title

      The Knee

      Volume: 25 Issue: 6 Pages: 1083-1090

    • DOI

      10.1016/j.knee.2018.06.003

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Arthroscopic anterior inferior iliac spine decompression does not alter postoperative muscle strength2018

    • Author(s)
      Tateishi Satoshi、Onishi Yasuo、Suzuki Hitoshi、Takahashi Makoto、Shiraishi Junichiro、Larson Christopher M.、Uchida Soshi
    • Journal Title

      Knee Surgery, Sports Traumatology, Arthroscopy

      Volume: 印刷中 Issue: 9 Pages: 2763-2771

    • DOI

      10.1007/s00167-018-5026-z

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Radiologic Correlation Between the Ischiofemoral Space and Morphologic Characteristics of the Hip in Hips With Symptoms of Dysplasia2018

    • Author(s)
      Ohnishi Yasuo, Suzuki Hitoshi, Nakashima Hirotaka, Murata Yoichi, Matsuda Dean K., Sakai Akinori, Uchida Soshi
    • Journal Title

      American Journal of Roentgenology

      Volume: 210(3) Issue: 3 Pages: 608-614

    • DOI

      10.2214/ajr.17.18465

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Endoscopic shelf acetabuloplasty can improve clinical outcomes and achieve return to sports-related activity in active patients with hip dysplasia2018

    • Author(s)
      Uchida Soshi、Hatakeyama Akihisa、Kanezaki Shiho、Utsunomiya Hajime、Suzuki Hitoshi、Mori Toshiharu、Chang Angela、Matsuda Dean K.、Sakai Akinori
    • Journal Title

      Knee Surgery, Sports Traumatology, Arthroscopy

      Volume: in press Issue: 10 Pages: 3165-3177

    • DOI

      10.1007/s00167-017-4787-0

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Arthroscopic Shoelace Side-to-Side Repair Technique Using Ultratape for the Treatment of Longitudinal Midsubstance Rotator Cuff Tears2017

    • Author(s)
      Suzuki Hitoshi、Chang Angela、Kumagae Hiroto、Shimizu Yuki、Sakai Akinori、Uchida Soshi
    • Journal Title

      Arthroscopy Technique

      Volume: 6 Issue: 5 Pages: e1845-e1850

    • DOI

      10.1016/j.eats.2017.06.058

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Arthroscopic Technique to Reduce Suture Button Migration During Anterior Cruciate Ligament Reconstruction Procedure2017

    • Author(s)
      Ohnishi Yasuo、Chang Angela、Utsunomiya Hajime、Suzuki Hitoshi、Nakamura Eiichiro、Sakai Akinori、Uchida Soshi
    • Journal Title

      Arthroscopy Technique

      Volume: 6 Issue: 5 Pages: e1927-e1931

    • DOI

      10.1016/j.eats.2017.07.016

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparison of the induction of c- fos -eGFP and Fos protein in the rat spinal cord and hypothalamus resulting from subcutaneous capsaicin or formalin injection2017

    • Author(s)
      Motojima Yasuhito、Matsuura Takanori、Yoshimura Mitsuhiro、Hashimoto Hirofumi、Saito Reiko、Ueno Hiromichi、Maruyama Takashi、Sonoda Satomi、Suzuki Hitoshi、Kawasaki Makoto、Ohnishi Hideo、Sakai Akinori、Ueta Yoichi
    • Journal Title

      Neuroscience

      Volume: 356 Pages: 64-77

    • DOI

      10.1016/j.neuroscience.2017.05.015

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] カラゲニン誘発性膝関節炎ラットにおける視床下部-下垂体系および視床下部-脊髄系の侵害受容調節の検討2020

    • Author(s)
      西村 春来、川崎 展、元嶋 尉士、松浦 孝紀、馬場 一彦、鈴木 仁士、山中 芳亮、大西 英生、吉村 充弘、丸山 崇、園田 里美、西村 和朗、田中 健太郎、上田 陽一、酒井 昭典
    • Organizer
      第49回日本心脈管作動物質学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] カラゲニン誘発性膝関節炎ラットにおける視床下部-下垂体系および視床下部-脊髄系の侵害受容調節の検討2020

    • Author(s)
      西村 春来、川崎 展、元嶋 尉士、松浦 孝紀、馬場 一彦、鈴木 仁士、山中 芳亮、大西 英生、吉村 充弘、丸山 崇、園田 里美、西村 和朗、田中 健太郎、上田 陽一、酒井 昭典
    • Organizer
      第97回日本生理学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Neuropathic Pain Upregulates the Hypothalamo-neurohypophysial/-spinal Oxytocinergic Pathways in the Oxytocin-mRFP1 Transgenic Rat.2019

    • Author(s)
      Kawasaki M, Nishimura H, Matsuura T, Suzuki H, Ohnishi H, Yamanaka Y, Ueta Y, Sakai A
    • Organizer
      65th Orthopaedic Research Society
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] カラゲニン誘発性膝関節炎ラットにおける視床下部-下垂体系および視床下部-脊髄系の侵害受容調節の検討2019

    • Author(s)
      川崎展、西村春来、元嶋尉士、松浦孝紀、鈴木仁士、大西英生、上田陽一
    • Organizer
      第63回日本リウマチ学会・学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] オキシトシン-mRFP1トランスジェニックラットを用いた神経障害性疼痛モデルにおける中枢神経系生理活性について2019

    • Author(s)
      西村 春来、川崎 展、松浦 孝紀、元嶋 尉士、鈴木 仁士、山中 芳亮、大西 英生、上田 陽一、酒井 昭典
    • Organizer
      第34回日本整形外科基礎学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] オキシトシン-mRFP1トランスジェニックラットを用いた神経障害性疼痛モデルにおける中枢神経系生理活性について2018

    • Author(s)
      西村春来、川﨑展、元嶋尉士、鈴木仁士、大西英生、吉村充弘、丸山崇、齋藤玲子、上野啓通、園田里美、西村和朗、田中健太郎、上田陽一、酒井昭典
    • Organizer
      第40回日本疼痛学会
    • Related Report
      2018 Research-status Report
  • [Presentation] c-fos-eGFPトランスジェニックラットを用いた膝関節炎モデルにおける中枢神経系生理活性の解明2018

    • Author(s)
      西村春来、川﨑展、元嶋尉士、鈴木仁士、大西英生、上田陽一
    • Organizer
      第62回日本リウマチ学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] オキシトシン-mRFP1トランスジェニックラットを用いた神経障害性疼痛モデルにおける中枢神経系生理活性について2018

    • Author(s)
      西村春来, 川崎展, 元嶋尉士, 鈴木仁士, 大西英生, 吉村充弘, 丸山崇,齋藤玲子,上野啓通,園田里美, 西村和朗, 田中健太郎,上田陽一,酒井昭典
    • Organizer
      第13回環境生理学プレコングレス
    • Related Report
      2017 Research-status Report
  • [Presentation] 複合性局所疼痛症候群の既往があり、膝関節後内側に再発した滑膜性軟骨腫症の鏡視下手術治療経験2018

    • Author(s)
      高田真一朗, 畠山昌久, 鈴木仁士, 内田宗志
    • Organizer
      第44回九州膝関節研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] Fluorescent visualization of oxytocin neurons activated by acute nociceptive stimuli in the c-fos-eGFP transgenic rats2017

    • Author(s)
      Yasuhito Motojima, Haruki Nishimura, Takanori Matsuura, Mitsuhiro Yoshimura, Hirofumi Hashimoto, Reiko Saito, Hiromichi Ueno, Takashi Maruyama, Satomi Sonoda, Kazuaki Nishimura, Kentaro Tanaka, Hitoshi Suzuki, Makoto Kawasaki, Hideo Ohnishi, Akinori Sakai, Yoichi Ueta
    • Organizer
      Fourth World Congress of Reproductive Biology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] プロ・大学サッカー選手におけるfemoroacetabular impingement(FAI)と第5中足骨疲労骨折の関連2017

    • Author(s)
      清水勇樹, 綿貫誠, 宇都宮啓, 林英俊, 熊谷達仁, 鈴木仁士, 内田宗志, 酒井昭典
    • Organizer
      第90回日本整形外科学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 膝離断性骨軟骨炎に対する保存療法の成績2017

    • Author(s)
      上野仁豪, 鈴木仁士, 中島裕貴, 内田宗志
    • Organizer
      第9回日本関節鏡・膝・スポーツ整形外科学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 上腕骨外上顆炎のECRBリリース術後に生じた後外側不安定症に対して、docking法を用いて後外側靭帯再建術を施行した治療経験2017

    • Author(s)
      德田昂太郎, 鈴木仁士, 雪澤洋平, 大西康央, 熊谷達仁, 清水勇樹, 内田宗志
    • Organizer
      第9回日本関節鏡・膝・スポーツ整形外科学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 外傷性肩関節脱臼に肩甲下筋腱断裂および上腕二頭筋長頭腱脱臼を伴った鏡視下手術治療経験2017

    • Author(s)
      嵐智哉, 熊谷達仁, 本田英三郎, 鈴木仁士, 内田宗志
    • Organizer
      第9回日本関節鏡・膝・スポーツ整形外科学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 寛骨臼形成不全症股(DDH)に発症したRim fracture(RF)に関節鏡視下整復固定術と鏡視下臼蓋形成術を行った3例2017

    • Author(s)
      清水勇樹, 雪澤洋平, 大西康央, 熊谷達仁, 鈴木仁士, 内田宗志
    • Organizer
      第9回日本関節鏡・膝・スポーツ整形外科学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 股関節滑膜性脂肪腫症に対する股関節鏡視下手術の治療経験2017

    • Author(s)
      西村春来, 鈴木仁士, 大西康央, 内田宗志
    • Organizer
      第9回日本関節鏡・膝・スポーツ整形外科学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 体重200kg超級の相撲力士に対する鏡視下FAI手術の治療経験2017

    • Author(s)
      雪澤洋平, 鈴木仁士, 清水勇樹, 熊谷達仁, 岩元俊樹, 德田昂太郎, 内田宗志
    • Organizer
      第44回日本股関節学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Ischiofemoral space はFAI患者と比較して、DDH患者で有意に狭小化する2017

    • Author(s)
      大西康央, 中島裕貴, 鈴木仁士, 内田宗志
    • Organizer
      第44回日本股関節学会学術集会
    • Related Report
      2017 Research-status Report

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

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