Investigation of a role for multifunctional mechanosensor TRPV2 in adult sensory neuron and pain

• Project/Area Number: 24590725
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pain science
• Research Institution: Chubu University (2014); Nagoya University (2012-2013)
• Principal Investigator: KATANOSAKA Kimiaki 中部大学, 生命健康科学部, 准教授 (50335006)
• Co-Investigator(Renkei-kenkyūsha): TAGUCHI Toru 名古屋大学, 環境医学研究所, 助教 (90464156) ; KATANOSAKA Yuki 岡山大学, 大学院医歯薬学総合研究科, 助教 (60432639)
• Research Collaborator: NARUSE Keiji 岡山大学, 大学院医歯薬学総合研究科, 教授 ; TAKATSU Satomi 岡山大学, 大学院医歯薬学総合研究科, 博士研究員 ; MIZUMURA Kazue 中部大学, 生命健康科学部, 教授
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: TRPV2 / 疼痛 / 機械受容 / 侵害受容器 / 一次知覚神経 / 脊髄神経節 / 痛覚 / 熱痛覚

Outline of Final Research Achievements

In this research, we explored an unknown function of TRPV2, a nonselective cation channel, in adult primary sensory neurons by construction and analysis of a primary sensory neuron-specific conditional knock-out mice of TRPV2 (cKO). There was no apparent difference in number, population, and morphology of the primary sensory neurons, and their axonal development between the cKO mice and normal littermates. However, the nocifensive behavior of the mice against noxious mechanical stimuli and the incidence of stretch-sensitive primary sensory neurons with relatively high-thresholds were significantly reduced in cKO mice compared to the normal mice. These results suggest that TRPV2 in the adult primary sensory neurons is involved in the mechanical nociception.

Research Products

• [Journal Article] Peripheral and spinal mechanisms of nociception in a rat reserpine-induced pain model. (2015)
  • Author(s): Taguchi T, Katanosaka K, Yasui M, Hayashi K, Yamashita M, Wakatsuki K, Kiyama H, Yamanaka A, Mizumura K.
  • Journal Title: Pain Volume: 156 Issue: 3 Pages: 415-427
  • DOI: 10.1097/01.j.pain.0000460334.49525.5e
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] TRPV2 is critical for the maintenance of cardiac structure and function in mice. (2014)
  • Author(s): Katanosaka Y, Iwasaki K, Ujihara Y, Takatsu S, Nishitsuji K, Kanagawa M, Sudo A, Toda T, Katanosaka K, Mohri S, Naruse K.
  • Journal Title: Nat Comm Volume: 5 Issue: 1 Pages: 3932-3932
  • DOI: 10.1038/ncomms4932
  • NAID: 120005690060
  • Peer Reviewed / Open Access
• [Journal Article] TRPV1 and TRPV4 play pivotal roles in delayed onset muscle soreness. (2013)
  • Author(s): H. Ota, K. Katanosaka, S. Murase, M. Kashio, M. Tominaga, and K. Mizumura.
  • Journal Title: PLoS.ONE Volume: ８ Issue: 6 Pages: e65751-e65751
  • DOI: 10.1371/journal.pone.0065751
  • Peer Reviewed
• [Presentation] The immunohistochemical characterization of the new heat-sensitive primary sensory neuron in mouse dorsal root ganglia. (2015)
  • Author(s): Katanosaka K, Takeda K, Katanosaka Y, Kashio M, Tominaga M, Mizumura K
  • Organizer: 第92回日本生理学会大会
  • Place of Presentation: 神戸国際会議場（兵庫県・神戸市）
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] 成体一次感覚ニューロンに発現するTRPV2の機械痛覚における役割 (2014)
  • Author(s): 片野坂公明, 高津理美, 水村和枝, 成瀬恵治, 片野坂友紀
  • Organizer: 平成26年度生理学研究所研究会『痛みと痛覚情動連関の神経機構』
  • Place of Presentation: 生理学研究所（愛知県・岡崎市）
  • Year and Date: 2014-12-10 – 2014-12-11
• [Presentation] 組織特異的遺伝子欠損マウスを用いた成体一次知覚神経でのTRPV2の生理的機能の解析 (2014)
  • Author(s): 片野坂公明，高津理美，水村和枝，成瀬恵治，片野坂友紀
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島大学郡元キャンパス
• [Presentation] 伸展刺激誘発性カルシウム応答の解析による機械感受性一次求心性ニューロンの分類 (2013)
  • Author(s): 片野坂公明，高津理美, 成瀬恵治, 片野坂友紀
  • Organizer: 第36回日本神経科学会大会 (Neuro2013)
  • Place of Presentation: 国立京都国際会議場
• [Presentation] 培養DRGニューロンのストレッチ応答へのTRPV2 の関与 (2013)
  • Author(s): 片野坂公明，高津理美, 成瀬恵治, 片野坂友紀
  • Organizer: 第６０回中部日本生理学会
  • Place of Presentation: 岐阜大学
• [Presentation] TRPV1- and V2-negative Heat-sensitive Primary Afferent Neurons in Mouse Dorsal Root Ganglia (2013)
  • Author(s): Kimiaki Katanosaka, Kazuhiro Takeda, Yuki Katanosaka, Satomi Takatsu, Makiko Kashio, Makoto Tominaga, Kazue Mizumura
  • Organizer: The 5th Asian Pain Symposium
  • Place of Presentation: Okazaki Conference Center
• [Presentation] Immunohistochemical detection of heat-sensitive primary afferent neurons and their correlation with transient receptor potential vanilloid 1 and 2 in mice． (2012)
  • Author(s): 片野坂公明, 竹田和弘, 片野坂友紀, 高津理美, 加塩麻紀子, 富永真琴, 水村和枝
  • Organizer: 日本比較生理生化学会第34回大会
  • Place of Presentation: 総合研究大学院大学 葉山キャンパス
• [Presentation] マウス高温感受性一次知覚ニューロンの免疫組織化学的探索 (2012)
  • Author(s): 片野坂公明
  • Organizer: 第4回光操作研究会
  • Place of Presentation: 自然科学研究機構 岡崎カンファレンスセンター
• [Presentation] Involvement of TRPV1 and TRPA1 in the generation of mechanical hyperalgesia after exercise (delayed onset muscle soreness, DOMS). (2012)
  • Author(s): 太田大樹、片野坂公明、加塩麻紀子、富永真琴、水村和枝
  • Organizer: 第35回日本神経科学会大会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] Chondroitin sulfate proteoglycan is involved in low pH-induced sensitization of mechanical response in cultured IB4-positive nociceptive dorsal root ganglion neurons of rats. (2012)
  • Author(s): 久保亜抄子、片野坂公明、水村和枝
  • Organizer: 第35回日本神経科学会大会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] A role for transient receptor potential vanilloid 2 in mechanical nociception and a stretch-evoked response of primary afferent neurons. (2012)
  • Author(s): 片野坂公明，高津理美，水村和枝, 成瀬恵治, 片野坂友紀
  • Organizer: 第35回日本神経科学会大会
  • Place of Presentation: 名古屋国際会議場