The elucidation of molecular mechanism for the physiologically active substance in the brain induced by pain stress using transgenic animal model

• Project/Area Number: 25462391
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: KAWASAKI Makoto 産業医科大学, 医学部, 講師 (40644860)
• Co-Investigator(Kenkyū-buntansha): UETA Yoichi 産業医科大学, 医学部医学科, 教授 (10232745)
• Co-Investigator(Renkei-kenkyūsha): SAKAI Akinori 産業医科大学, 医学部医学科, 教授 (90248576) ; MORI Toshiharu 産業医科大学, 医学部医学科, 講師 (80525444) ; Sabanai Ken 産業医科大学, 医学部医学科, 助教 (70644863) ; HASHIMOTO Hirofumi 産業医科大学, 医学部医学科, 准教授 (10454935)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: オキシトシンによる疼痛調整作用 / 急性炎症ストレス / 慢性炎症ストレス / トランスジェニックラット / 神経内分泌 / 関節リウマチ / オキシトシン / 疼痛 / 神経内分泌学

Outline of Final Research Achievements

Oxytocin (OXT) as one of neurohypophysial hormones is suggested to play an important role in pain modulation. OXT binding sites, as well as OXT receptor expression are located in the dorsal horn of spinal cord in rats. A population of parvocellular OXTergic neurons of the paraventricular nucleus project to the spinal cord. However, little is known about the neuronal networks responsible for OXT effects. In the present study, using OXT-monomeric red fluorescent protein 1 (mRFP1) transgenic rats, we examined the response to acute (by formalin test) and chronic (by induced adjuvant arthritis) nociception in rat models. The OXT-mRFP1 expression in the hypothalamic paraventricular nucleus (PVN), posterior pituitary and spinal cord were significantly increased in acute and chronic nociceptive models in rats. The results suggest that OXT expression was up-regulated by acute and chronic inflammatory stress, and also that OXT in the PVN-spinal pathway may be involved in pain sensory modulation.

Research Products

• [Journal Article] Effects of peripherally administered cholecystokinin-8 and secretin on feeding/drinking and oxytocin-mRFP1 fluorescence in transgenic rats. (2016)
  • Author(s): Motojima Y, Kawasaki M, Matsuura T, Saito R, Yoshimura M, Hashimoto H, Ueno H, Maruyama T, Suzuki H, Ohnishi H, Sakai A, Ueta Y
  • Journal Title: Neuroscience Research Volume: 印刷中 Pages: 63-69
  • DOI: 10.1016/j.neures.2016.02.005
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Effects of central administration of oxytocin-saporin cytotoxin on chronic inflammation and feeding/drinking behaviors in adjuvant arthritic rats. (2016)
  • Author(s): Matsuura T, Kawasaki M, Hashimoto H, Yoshimura M, Motojima Y, Saito R, Ueno H, Maruyama T, Sabanai K, Mori T, Ohnishi H, Sakai A, Ueta Y
  • Journal Title: Neuroscience Letters Volume: 621 Pages: 104-110
  • DOI: 10.1016/j.neulet.2016.04.010
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Fluorescent visualisation of oxytocin in the hypothalamo-neurohypophysial/-spinal pathways after chronic inflammation in oxytocin-monmeric red fluorescent protein 1 transgenic rats. (2015)
  • Author(s): Matsuura, T. Kawasaki, M . Hashimoto, H. Ishikura, T. Yoshimura, M. Ohkubo, JI. Maruyama, T. Motojima, Y. Sabanai, K. Mori, T. Ohnishi, H. Sakai, A. & Ueta, Y.
  • Journal Title: Journal of Neuroendocrinology Volume: 27(7) Issue: 7 Pages: 636-646
  • DOI: 10.1111/jne.12290
  • Peer Reviewed
• [Journal Article] Possible involvement of TRPV1 and TRPV4 in nociceptive stimulation-induced nocifensive behavior and neuroendocrine response in mice. (2015)
  • Author(s): Ishikura, T. Suzuki, H. Shoguchi, K. Koreeda, Y. Aritomi, T. Matsuura, T. Yoshimura, M. Ohkubo, JI. Maruyama, T. Kawasaki, M. Ohnishi, H. Sakai, A. Mizuki, M. & Ueta, Y.
  • Journal Title: Brain Rsearch Bulletin Volume: 118 Pages: 7-16
  • DOI: 10.1016/j.brainresbull.2015.08.004
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] ストレス調節ホルモンとしてのオキシトシンの役割 (2015)
  • Author(s): 上田陽一
  • Journal Title: ストレス科学 Volume: 29 Pages: 366-372
• [Presentation] Electrophysiological study combined with fluorescent visualization in rat vasopressin / oxytocin neuron. (2015)
  • Author(s): Ueta Y
  • Organizer: Neuropeptides and Neurotransmitters : Role in Physiology and Pathophysiology & Second Meeting of Indian Sub-continental Branch of the International Neuropeptide Society.
  • Place of Presentation: Bhubaneswar, India
  • Year and Date: 2015-12-13
  • Invited
• [Presentation] Possible involvements of TRPV1 and TRPV4 in neuroendocrine response and drinking behavior. (2015)
  • Author(s): Ueta Y, Matsuura T, Motojima Y, Yoshimura M, Shoguchi K, Maruyama T, Hashimoto H, Ishikura T, Kawasaki M, Ohnishi H, Sakai A
  • Organizer: The 13th International Symposium on Molecular and Neural Machanisms of Taste and Olfactory Perception
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2015-11-03
• [Presentation] ラット視床下部オキシトシンニューロン-延髄下行系の摂食抑制性消化管ペプチドによる活性化の蛍光タンパクによる可視化の定量評価 (2015)
  • Author(s): 元嶋尉士、上田陽一
  • Organizer: 第68回日本自律神経学会総会
  • Place of Presentation: ウインクあいち（名古屋市）
  • Year and Date: 2015-10-29
• [Presentation] アジュバンド関節炎モデルラットにおける下垂体後葉系および視床下部-脊髄系のオキシトシンの役割 (2015)
  • Author(s): 松浦孝紀、元嶋尉士、上野啓通、齋藤玲子、吉村充弘、橋本弘史、鈴木仁士、川崎展、大西英生、酒井昭典、上田陽一
  • Organizer: 第66回西日本生理学会
  • Place of Presentation: 久留米大学筑水会館（久留米市）
  • Year and Date: 2015-10-09
• [Presentation] 急性炎症・疼痛モデルラットにおける下垂体後葉系および視床下部‐脊髄系のオキシトシンの分子基盤の解明～遺伝子改変動物を用いた検討～ (2015)
  • Author(s): 川崎展、松浦孝紀、元嶋尉士、橋本弘史、尾仲達史、酒井昭典、上田陽一
  • Organizer: 第33回産業医科大学学会
  • Place of Presentation: 産業医科大学（北九州市）
  • Year and Date: 2015-10-03
• [Presentation] TRPV1およびTRPV4ノックアウトマウスにおける浸透圧・非浸透圧刺激後の飲水行動の検討 (2015)
  • Author(s): 元嶋尉士、松浦孝紀、齋藤玲子、上野啓通、吉村充弘、橋本弘史、鈴木仁士、川崎展、大西英生、酒井昭典、上田陽一
  • Organizer: 第25回日本病態生理学会
  • Place of Presentation: 愛媛大学城北キャンパス（松山市）
  • Year and Date: 2015-07-31
• [Presentation] Effects of osmotic and non-osmotic stimuli on drinking behavior in TRPV1 and TRPV4 knockout mice. (2015)
  • Author(s): Ueta Y, Matsuura T, Motojima Y, Yoshimura M, Shoguchi K, Maruyama T, Hashimoto H, Kawasaki M, Ohnishi H, Sakai A
  • Organizer: International Behavioral Neuroscience Society 2015
  • Place of Presentation: Victoria, Canada
  • Year and Date: 2015-06-02
  • Int'l Joint Research
• [Presentation] 急性炎症・疼痛モデルラットでの視床下部および脊髄におけるオキシトシン－単量体赤色蛍光タンパク1融合遺伝子の発現動態ならびにその役割について (2015)
  • Author(s): 松浦孝紀、川崎展、元嶋尉士、鈴木仁士、大西英生、上田陽一
  • Organizer: 第59回日本リウマチ学会総会・学術集会
  • Place of Presentation: 名古屋国際会議場（名古屋市）
  • Year and Date: 2015-04-23
• [Presentation] The expression of the oxytocin-monomeric red fluorescent protein 1 fusion gene in the hypothalamus and spinal cord of adjuvant-induced arthritic rats. (2013)
  • Author(s): Matsuura T, Ishikura T, Yoshimura M, Ohkubo J, Maruyama T, Kawasaki M, Ohnishi H, Hashimoto H, Ueta Y
  • Organizer: Neuroscience 2013
  • Place of Presentation: San Diego, CA, USA（サンディエゴコンベンションセンター）
• [Presentation] アジュバント関節炎における視床下部と脊髄後角でのオキシトシン発現動態の可視化 (2013)
  • Author(s): 松浦孝紀、川崎展、大西英生、上田陽一
  • Organizer: 第17回 日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 大阪（千里ライフサイエンスセンター）