脊髄内C線維終末に発現する温度センサー機能と病態時変化の解明

• Project Area: Molecular interaction and modal shift of cellular sensors
• Project/Area Number: 21026022
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kumamoto Health Science University
• Principal Investigator: 吉村 恵 (吉村 惠) 熊本保健科学大学, 大学院・保健科学研究科, 教授 (10140641)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥5,800,000 (Direct Cost: ¥5,800,000); Fiscal Year 2010: ¥2,900,000 (Direct Cost: ¥2,900,000); Fiscal Year 2009: ¥2,900,000 (Direct Cost: ¥2,900,000)
• Keywords: 熱刺激受容体 / 感作 / 慢性炎症 / in vivoパッチクランプ記録 / 熱応答 / 温度感受性 / 可塑性 / 膠様質細胞 / TRPV1 / TRPA1 / 温度受容器 / 受容体の感作 / 炎症関連物質 / 脊髄後角 / 脊髄スライス標本 / 自発性EPSC

Research Abstract

脊髄スライス標本を用いた研究から、熱受容体であるTRPV1はC線維の末梢のみならず中枢側にも発現しており、何らかの役割をはたしているものと考えられた。そこで、C線維の多く終末している膠様質細胞からin vivoパッチクランプ記録行い、末梢に加えた熱に応答するか否かを調べた。その結果、いずれの細胞も熱刺激には応答せず、中枢側に発現するTRPV1の意義は不明であった。そこで、慢性炎症モデルラット脊髄スライス標本を用いて同様に膠様質細胞から記録を行い、脊髄への直接熱刺激に対して如何なる温度感受性を示すかを正常ラットのそれと比較検討した。正常ラット脊髄スライスでは脊髄灌流Krebs液の温度を43oC以上にすると自発性EPSCの頻度の増大と緩徐な内向き電流が記録された。しかし、42oC以下の温度では何ら作用を示さなかった。次に慢性炎症ラット脊髄スライス標本から記録を行い、温度を変化させると、38oCから自発性EPSCの増大と緩徐な内向き電流が観察された。これらの結果は、慢性炎症モデルではTRPV1受容体が感作を起こし、より低い温度でも活性化されることが示唆された。

Research Products

• [Journal Article] Bone cancer pain induces a unique central sensitization through synaptic changes in a wide area of the spinal cord (2010)
  • Author(s): Yanagisawa Y, Furue H, Kawamata T Uta D, Yamamoto J, Furuse S, Katfuchi T, Imoto K, Iwamoto Y, Yoshimura M
  • Journal Title: Molecular Pain Volume: 6(On line journal)
  • Peer Reviewed
• [Journal Article] TRPA1-expressing primary afferents synapse with morphologically identifie113d subtypes of substantia gelatinosa neurons in the adult rat spinal cord (2010)
  • Author(s): Uta D, Furue H, Pickering AE, Rashid MDH, Mizuguchi-Takase H, Katafuchi T, Yoshimura M.
  • Journal Title: European Journal of Neuroscience Volume: 31(11) Pages: 1960-1973
  • Peer Reviewed
• [Journal Article] Enhancement of GABAergic tonic currents by midazolam and noradrenaline in rat substantia gelantinosa neurons in vitro. (2010)
  • Author(s): Maeda A, Katafuchi T, Oba Y, Shiokawa H, Yoshimura M.
  • Journal Title: Anesthesiology Volume: 113(2) Pages: 429-437
  • Peer Reviewed
• [Journal Article] TRPA1-expressing primary afferents synapse with morphologically identifird subtypes f substantia gelatinosa neurons in the adult rat spinal cord (2010)
  • Author(s): Uta D, Furue H, Pickering AE, Rashid MDH, Mizuguchi-Takase H, Katafuchi T, Yoshimura M.
  • Journal Title: European Journal of Neuroscience (In press)
  • Peer Reviewed
• [Journal Article] Enhancement of GABAergic tonic currents by midazolam and noradrenaline in rat substantia gelantinosa neurons in vitro (2010)
  • Author(s): Maeda A, Katafuchi T, Oba Y, Shiokawa H, Yoshimura M.
  • Journal Title: Anesthesiology (In press)
  • Peer Reviewed
• [Journal Article] Organization of intra- and translaminar neuronal connectivity in the superficial spinal dorsal horn (2009)
  • Author(s): Kato G, Kawasaki Y, Koga K, Uta D, Kosugi M, Yasaka T, Yoshimura M, Ji RR, Strassman AM.
  • Journal Title: Journal of Neuroscience 29(16) Pages: 5088-5099
  • Peer Reviewed
• [Journal Article] Actions of propofol on substantia gelatinosa neurones in rat spinal cord revealed by in vitro and in vivo patch-clamp recordings (2009)
  • Author(s): Takazawa T, Furue H, Nishikawa K, Uta D, Takeshima K, Goto F, Yoshimura M.
  • Journal Title: European Journal of Neuroscience 29(3) Pages: 518-528
  • Peer Reviewed
• [Journal Article] Responses to 5-HT morphologically identified neurons in the rat substantia gelatinosa in vitro (2009)
  • Author(s): Abe K, Kato G, Katafuchi T, Tamae A, Furue H, Yoshimura M.
  • Journal Title: Neuroscience 159(1) Pages: 316-324
  • Peer Reviewed
• [Presentation] Synaptic connection in the superficial dorsal horn revealed by laser photostimulation (2010)
  • Author(s): Yoshimura M, Uta D, Furue H, Hachisuka Y.
  • Organizer: 9^<th> Japan-Korea Joint Symposium, 2010, Kagoshima
  • Place of Presentation: 鹿児島
  • Year and Date: 2010-09-27
• [Presentation] 痛みを考える-最新感覚受容器研究に基づいて- (2010)
  • Author(s): 吉村惠
  • Organizer: 第12回日本カイロプラスティック徒手医学会
  • Place of Presentation: 福岡
  • Year and Date: 2010-09-05
• [Presentation] 慢性炎症性疼痛発生におけるBDNFの関与と脊髄内感覚回路の可塑性 (2010)
  • Author(s): 吉村惠
  • Organizer: 情報技術協会シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2010-04-27
• [Presentation] Effects of acupucture on the inhibitory transmission in the spinal cord (2009)
  • Author(s): Yoshimura M
  • Organizer: The 36^<th> Congress of the International Union of Physiological Sciences
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2009-07-29
• [Presentation] Responsiveness of C neurons in rat DRG and spinal dorsal horn neruons to 5-HT induced itch stimulation in vivo (2009)
  • Author(s): Yoshimura M
  • Organizer: 4^<th> International Conference of Neurons and Brain Diseases
  • Place of Presentation: Toronto, Canada
  • Year and Date: 2009-07-22
• [Presentation] Sensory Neural network formation with RNA binding protein musashi2 deficient mice (2009)
  • Author(s): Shibata S, Sakakibara S-I, Furue H, Yoshimura M, Takagi T, Ohkuma R, Kuwako K-I, Okano H, Okano H
  • Organizer: The 36^<th> Congress of the International Union of Physiological Sciences
  • Place of Presentation: Kyoto, Japan
• [Presentation] Modulation of nociceptive synaptic transmission in the adult rat spinal dorsal horn via activation of TPA1 and TRPV1 (2009)
  • Author(s): Uta D, Furue H, Yoshimura M.
  • Organizer: The 36^<th> Congress of the International Union of Physiological Sciences
  • Place of Presentation: Kyoto, Japan
• [Presentation] Selective loss of presynaptic 5-HT inhibitory actions on spinal mechanical noxious synaptic transmission in ovariectomized rats in vivo (2009)
  • Author(s): Furue H, Ito A, Yoshimura M
  • Organizer: The 36^<th> Congress of the International Union of Physiological Sciences
  • Place of Presentation: Kyoto, Japan
• [Presentation] Plastic changes in spinal nociceptive transmission of bone cancer pain model mice (2009)
  • Author(s): Yanagisawa Y, Furue H, Kawamata T, Namiki A, Iwamoto Y, Yoshimura M
  • Organizer: The 36^<th> Congress of the International Union of Physiological Sciences
  • Place of Presentation: Kyoto, Japan
• [Presentation] Enhancement of excitatory synaptic transmission in the substantia gelatinosa of the spinal cord in a mouse model of bone cancer pain (2009)
  • Author(s): Yanagisawa Y, Furue H, Kawamata T, Uta D, Iwamoto Y, Imoto K, Yoshimura M
  • Organizer: Society for Neuroscience
  • Place of Presentation: Chicago, USA
• [Presentation] Actions of TRPA1 and TRPV1 agonists on synaptic transmission in substantia gelatinosa neurons of the adult rat spinal cord (2009)
  • Author(s): Uta D, Furue H, Imoto K, Yoshimura M
  • Organizer: Society for Neuroscience
  • Place of Presentation: Chicago, USA
• [Presentation] Actions of endothelin-1 on nociceptive transmission in substantia gelatinosa of the adult mouse spinal cord (2009)
  • Author(s): Nishikawa Y, Uta D, Sasaki A, Andouh T, Furue H, Yoshimura M, Kuraishi Y
  • Organizer: Society for Neuroscience
  • Place of Presentation: Chicago, USA