Conversion of touch sensation to pain by the modal shift of sensor function

• Project Area: Molecular interaction and modal shift of cellular sensors
• Project/Area Number: 18077002
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: TANABE Tsutomu Tokyo Medical and Dental University, 大学院・医歯学総合研究科, 教授 (70183069)
• Project Period (FY): 2006 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥62,900,000 (Direct Cost: ¥62,900,000); Fiscal Year 2010: ¥12,600,000 (Direct Cost: ¥12,600,000); Fiscal Year 2009: ¥12,600,000 (Direct Cost: ¥12,600,000); Fiscal Year 2008: ¥13,700,000 (Direct Cost: ¥13,700,000); Fiscal Year 2007: ¥12,900,000 (Direct Cost: ¥12,900,000); Fiscal Year 2006: ¥11,100,000 (Direct Cost: ¥11,100,000)
• Keywords: 分子センサー / 触覚 / 神経因性疼痛 / アロディニア / 痛覚過敏 / 細胞感覚 / 分子センター

Research Abstract

We searched for the molecules which induce conversion of touch sensation to pain by the modal shift of their sensor functions. We identified μ-opioid, peripheral-type benzodiazepine receptor, and casein kinase 1ε as effectors which are functionally located downstream of N-type calcium channel activation. We also clarified how the modal shift of these molecules affect the excitability of neurons and their intracellular calcium transient [Ca^<2+>]i , and how the inhibitor of each molecule affects the observed changes caused by the modal shift of these molecules.

Research Products

• [Journal Article] Peripheral-type benzodiazepine receptor antagonist is effective in relieving neuropathic pain in mice. (2009)
  • Author(s): Kondo, D., Saegusa, H., Yabe, R., Takasaki, I., Kurihara, T., Zong, S., Tanabe, T.
  • Journal Title: J.Pharmacol.Sci. 110 Pages: 55-63
  • NAID: 10025736602
  • Peer Reviewed
• [Journal Article] Deficit of heat shock transcription factor 1-heat shock 70kDa protein 1A axis determines the cell death vulnerability in a model of spinocerebellar ataxia type 6. (2009)
  • Author(s): Li, L., Saegusa, H., Tanabe, T.
  • Journal Title: Genes to Cells 14 Pages: 1253-1269
  • Peer Reviewed
• [Journal Article] Upregulation of casein kinase 1 epsilon in dorsal root ganglia and spinal cord after mouse spinal nerve injury contributes to neuropathic pain. (2009)
  • Author(s): Sakurai, E., Kurihara, T., Kouchi, K., Saegusa, H., Zong, S., Tanabe, T.
  • Journal Title: Molecular Pain 5 Pages: 74-74
  • Peer Reviewed
• [Journal Article] Peripheral-type benzodiazepine receptor antagonist is effective in relieving neuropathic pain in mice (2009)
  • Author(s): Kondo, D., Saegusa, H., Yabe, R., Takasaki, I., Kurihara, T., Zong, S., Tanabe, T.
  • Journal Title: J Pharmacol.Sci. 110 Pages: 55-63
  • NAID: 10025736602
  • Peer Reviewed
• [Journal Article] Deficit of heat shock transcription factor 1-heat shock 70kDa protein 1A axis determines the cell death vulnerability in a model of spinocerebellar ataxia type 6 (2009)
  • Author(s): Li, L., Saegusa, H., Tanabe, T.
  • Journal Title: Genes to Cells 14 Pages: 1253-1269
  • Peer Reviewed
• [Journal Article] Upregulation of casein kinase 1 epsilon in dorsal root ganglia and spinal cord after mouse spinal nerve injury contributes to neuropathic pain (2009)
  • Author(s): Sakurai, E., Kurihara, T., Kouchi, K., Saegusa, H., Zong, S., Tanabe, T.
  • Journal Title: Molecular Pain 5 Pages: 74-74
  • Peer Reviewed
• [Journal Article] Properties of human Cav2.1 channel with a spinocerebellar ataxia type 6 mutation expressed in Purkinje cells. (2007)
  • Author(s): Saegusa, H., Wakamori, M., Matsuda, Y., Wang, J., Mori, Y., Zong, S., Tanabe, T.
  • Journal Title: Molec.Cell.Neurosci. 34 Pages: 261-270
  • Peer Reviewed
• [Journal Article] Properties of human Cav2.1 channel with a spinocerebellar ataxia type 6 mutation expressed in Purkinje cells (2007)
  • Author(s): Saegusa, H., Wakamori, M., Matsuda, Y., Wang, J., Mori, Y., Zong, S. and Tanabe, T
  • Journal Title: Mol. Cell. Neurosci 34 Pages: 261-270
  • Peer Reviewed
• [Journal Article] Properties of human Ca_v2.1 channel with a spinocerebellar ataxia type 6 mutation expressed in Purkinje cells (2007)
  • Author(s): Saegusa, H., Wakamori, M., Matsuda, Y., Wang, J., Mori, Y., Zong, S. and Tanabe, T.
  • Journal Title: Mol. Cell. Neurosci 34 Pages: 261-270
  • Peer Reviewed
• [Journal Article] 創薬ターゲットとしての電位依存性Ca^<2+>チャネル (2007)
  • Author(s): 田邊 勉
  • Journal Title: 医学のあゆみ 233 Pages: 474-478
• [Journal Article] Properties of human Ca_v2.1 channel with a spinocerebellar ataxia type 6 mutation expressed in Purkinje cells. (2007)
  • Author(s): Saegusa, H.
  • Journal Title: Mol. Cell. Neurosci. 34 Pages: 261-270
• [Journal Article] Progesterone receptor antagonist is effective for relieving neuropathic pain. (2006)
  • Author(s): Kondo, D., Yabe, R., Kurihara, T., Saegusa, H., Zong, S., Tanabe, T.
  • Journal Title: Eur.J.Pharm. 541 Pages: 44-48
  • Peer Reviewed
• [Journal Article] Altered cerebellar function in mice lacking Cav2.3 Ca^<2+> channel. (2006)
  • Author(s): Osanai, M.., Saegusa, H., Kazuno, A., Nagayama, S., Hu, Q., Zong, S., Murakoshi, T., Tanabe, T.
  • Journal Title: Biochem.Biophys.Res.Commun. 344 Pages: 920-925
  • Peer Reviewed
• [Journal Article] Progesterone receptor antagonist is effective for relieving neuropathic pain (2006)
  • Author(s): Kondo, D., Yabe, R., Kurihara, T., Saegusa, H., Zong, S. and Tanabe, T
  • Journal Title: Eur. J. Pharm 541 Pages: 44-48
  • Peer Reviewed
• [Journal Article] Altered cerebellar function in mice lacking Ca_v2.3 Ca^<2+> channel. (2006)
  • Author(s): Osanai, M.
  • Journal Title: Biochem. Biophys. Res. Commun. 344 Pages: 920-925
• [Journal Article] Progesterone receptor antagonist is effective for relieving neuropathic pain. (2006)
  • Author(s): Kondo, D.
  • Journal Title: Eur. J. Pharm. 541 Pages: 44-48
• [Journal Article] Caチャネルと痛み伝達 (2006)
  • Author(s): 田邊 勉
  • Journal Title: 日薬理誌 127 Pages: 156-160
  • NAID: 10019251744
• [Journal Article] カルシウムチャネル (2006)
  • Author(s): 田邊 勉
  • Journal Title: Clinical Neuroscience 24 Pages: 730-731
• [Presentation] Activation of casein kinase 1δ/ε in dorsal root ganglia and spinal cord contributes to behavioral hypersensitivity induced by peripheral inflammation in mice (2011)
  • Author(s): Kurihara, T., Sakurai, E., Asada T., Miyata, A., Tanabe, T.
  • Organizer: 第84回日本薬理学会年会
  • Place of Presentation: Yokohama, Japan
• [Presentation] Upregulation of casein kinase 1ε in dorsal root ganglia and spinal cord contributes to neuropathic pain induced by spinal nerve ligation in mice (2011)
  • Author(s): Sakurai, E., Kurihara, T., Miyata, A., Tanabe, T.
  • Organizer: 第84回日本薬理学会年会
  • Place of Presentation: Yokohama, Japan
• [Presentation] Upregulation of casein kinase 1 epsilon after spinal nerve injury contributes to neuropathic pain (2010)
  • Author(s): Tsutomu Tanabe, Eri Sakurai, Takashi Kurihara, Kasumi Kouchi, Hironao Saegusa, Shuqin Zong
  • Organizer: The Third International Congress on Neuropathic Pain Athens
  • Place of Presentation: Greece
• [Presentation] Inhibitors of casein kinase 1 epsilon are effective in blocking pain in neuropathic mice without showing any appreciable side effect in normal mice (2010)
  • Author(s): Tsutomu Tanabe, Eri Sakurai, Takashi Kurihara, Kasumi Kouchi, Hironao Saegusa, Shuqin Zong
  • Organizer: The 40th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: San Diego, USA
• [Presentation] Upregulation of casein kinase 1 epsilon after spinal nerve injury contributes to neuropathic pain (2010)
  • Author(s): Tanabe, T., Sakurai, E., Kurihara, T., Kouchi, K., Saegusa, H., Zong, S.
  • Organizer: The Third International Congress on Neuropathic Pain
  • Place of Presentation: Athens, Greece
• [Presentation] Searching for downstream molecules of N-type voltage-dependent calcium channels (Cav2.2) contributing to the neuropathic pain (2010)
  • Author(s): Tanabe, T., Sakurai, E., Kurihara, T., Kouchi, K., Saegusa, H., Zong, S.
  • Organizer: 16th World Congress of Basic and Clinical Pharmacology
  • Place of Presentation: Copenhagen, Denmark
• [Presentation] Specific blockade of synaptic transmission and behavioral pain responses by casein kinase 1 epsilon inhibitors in neuropathic mice (2010)
  • Author(s): Tanabe, T., Sakurai, E., Kurihara, T., Kouchi, K., Saegusa, H., Zong, S.
  • Organizer: The 50th Annual Meeting of the American Society for Cell Biology
  • Place of Presentation: Philadelphia, USA
• [Presentation] Heat shock 70kDa protein 1A in a cellular model of spinocerebellar ataxia type 6 (2009)
  • Author(s): T.Tanabe, L.Li, H.Saegusa
  • Organizer: The 49th Annual Meeting of the Americal Society for Cell Biology
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2009-12-08
• [Presentation] Identification of the molecules determining cell death vulnerability in a cellular model of spinocerebellar ataxia type 6 (2009)
  • Author(s): T.Tanabe, L.Li, H.Saegusa
  • Organizer: The 39th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Chicago, IL, USA
  • Year and Date: 2009-10-20
• [Presentation] Enhanced stress-induced cell death in HEK293 cells expressing carboxyl-terminal portion of human Cav2.1 with a spinocerebellar ataxia type 6 mutation (2009)
  • Author(s): T. Tanabe, L. Li, and H. Saegusa
  • Organizer: Keystone Symposia : Neurodegenerative Diseases : New Molecular Mechanisms
  • Place of Presentation: Keystone CO, USA
  • Year and Date: 2009-02-20
• [Presentation] Co-administration of ATP attenuates peripheral type benzodiazepine receptor antagonist-induced antinociception of neuropathic pain (2008)
  • Author(s): T. Tanabe, D. Kondo, R. Yabe, I. Takasaki, T. Kurihara, H. Saegusa and S. Zong
  • Organizer: The 38th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2008-11-17
• [Presentation] Enhanced expression of peripheral-type benzodiazepine receptor induces neuropathic pain through the activation of microglia (2008)
  • Author(s): T. Tanabe, D. Kondo, R. Yabe, I. Takasaki, T. Kurihara, H. Saegusa and S. Zong
  • Organizer: The 3rd Asian Pain symposium
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2008-07-18
• [Presentation] Co-administration of ATP attenuates peripheral type benzodiazepine receptor antagonist-induced antinociception of neuropathic pain. (2008)
  • Author(s): T.Tanabe, D.Kondo, R.Yabe, I.Takasaki, T.Kurihara, H.Saegusa, S.Zong
  • Organizer: The 38th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Washington DC, USA
• [Presentation] Enhanced expression of peripheral-type benzodiazepine receptor induces neuropathic pain (2007)
  • Author(s): T. Tanabe, D. Kondo, R. Yabe, I. Takasaki, T. Kurihara, H. Saegusa and S. Zong
  • Organizer: The 36th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: San Diego CA, USA
  • Year and Date: 2007-11-07
• [Presentation] Enhanced expression of peripheral-type benzodiazepine receptor induces neuropathic pain. (2007)
  • Author(s): T.Tanabe, D.Kondo, R.Yabe, I.Takasaki, T.Kurihara, H.Saegusa, S.Zong
  • Organizer: The 36th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: San Diego CA, USA
• [Presentation] Involvement of steroid hormone receptors in the maintenance of neuropathic pain. (2006)
  • Author(s): T.Tanabe ; D.Kondo, I.Takasaki, R.Yabe, T.Kurihara, H.Saegusa, S.Zong
  • Organizer: The 35rd Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Atlanta, GA, USA
• [Remarks] ホームページ等
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• [Patent(Industrial Property Rights)] Therapeutic agent for neuropathic pain (2010)
  • Inventor(s): 田邊勉
  • Industrial Property Rights Holder: 東京医科歯科大学・JST
  • Acquisition Date: 2010-12-14
  • Overseas
• [Patent(Industrial Property Rights)] 神経因性疼痛治療剤 (2010)
  • Inventor(s): 田邊勉
  • Industrial Property Rights Holder: 東京医科歯科大学・JST
  • Acquisition Date: 2010-09-17
• [Patent(Industrial Property Rights)] 神経因性疼痛治療剤 (2009)
  • Inventor(s): 田邊勉
  • Industrial Property Rights Holder: 東京医科歯科大学・JST
  • Acquisition Date: 2009-12-25
• [Patent(Industrial Property Rights)] 神経因性疼痛治療剤 (2009)
  • Inventor(s): 田邊勉
  • Industrial Property Rights Holder: 東京医科歯科大学・JST
  • Acquisition Date: 2009-10-02
• [Patent(Industrial Property Rights)] 神経因性疼痛治療剤 (2009)
  • Inventor(s): 田邊勉
  • Industrial Property Rights Holder: 東京医科歯科大学・JST
  • Acquisition Date: 2009-08-21
• [Patent(Industrial Property Rights)] 神経因性疼痛治療剤 (2008)
  • Inventor(s): 田邊勉
  • Industrial Property Rights Holder: 東京医科歯科大学・JST
  • Acquisition Date: 2008-12-05
• [Patent(Industrial Property Rights)] 神経因性疼痛治療剤 (2008)
  • Inventor(s): 田邊勉
  • Industrial Property Rights Holder: 東京医科歯科大学・JST
  • Acquisition Date: 2008-11-28
• [Patent(Industrial Property Rights)] 神経因性疼痛治療剤 (2008)
  • Inventor(s): 田邊勉
  • Industrial Property Rights Holder: 東京医科歯科大学・JST
  • Acquisition Date: 2008-11-21
• [Patent(Industrial Property Rights)] 神経因性疼痛治療剤 (2008)
  • Inventor(s): 田邊勉
  • Industrial Property Rights Holder: 科学技術振興機構・東京医科歯科大学
  • Acquisition Date: 2008-11-28
• [Patent(Industrial Property Rights)] 神経因性疼痛治療剤 (2008)
  • Inventor(s): 田邊勉
  • Industrial Property Rights Holder: 科学技術振興機構・東京医科歯科大
  • Acquisition Date: 2008-11-21
• [Patent(Industrial Property Rights)] 神経因性疼痛治療剤 (2008)
  • Inventor(s): 田邊勉
  • Industrial Property Rights Holder: 科学技術振興機構・東京医科歯科大
  • Acquisition Date: 2008-11-28
• [Patent(Industrial Property Rights)] 神経因性疼痛治療剤 (2008)
  • Inventor(s): 田邊勉
  • Industrial Property Rights Holder: 科学技術振興機構・東京医科歯科大
  • Acquisition Date: 2008-12-05
• [Patent(Industrial Property Rights)] THERAPEUTIC AGENT FOR NEUROGENIC PAIN (2007)
  • Inventor(s): 田邊勉
  • Industrial Property Rights Holder: 東京医科歯科大学・JST
  • Filing Date: 2007-01-15
  • Overseas
• [Patent(Industrial Property Rights)] THERAPEUTIC AGENT FOR NEUROPATHIC PAIN (2007)
  • Inventor(s): 田邊勉
  • Industrial Property Rights Holder: 東京医科歯科大学・JST
  • Filing Date: 2007-01-15
  • Overseas
• [Patent(Industrial Property Rights)] Therapeutic agent for neuropathic pain (2007)
  • Inventor(s): 田邊勉
  • Industrial Property Rights Holder: 科学技術振興機構・東京医科歯科大学
  • Filing Date: 2007-01-15
  • Overseas
• [Patent(Industrial Property Rights)] THERAPEUTIC AGENT FOR NEUROGENIC PAIN (2006)
  • Inventor(s): 田邊勉
  • Industrial Property Rights Holder: 東京医科歯科大学・JST
  • Filing Date: 2006-09-26
  • Overseas
• [Patent(Industrial Property Rights)] THERAPEUTIC AGENT FOR NEUROPATHIC PAIN (2006)
  • Inventor(s): 田邊勉
  • Industrial Property Rights Holder: 東京医科歯科大学・JST
  • Filing Date: 2006-08-30
  • Overseas
• [Patent(Industrial Property Rights)] THERAPEUTIC AGENT FOR NEUROGENIC PAIN (2006)
  • Inventor(s): 田邊勉
  • Industrial Property Rights Holder: 東京医科歯科大学・JST
  • Filing Date: 2006-06-08
  • Overseas
• [Patent(Industrial Property Rights)] AGENT FOR TREATING NEUROPATHIC PAIN (2006)
  • Inventor(s): 田邊勉
  • Industrial Property Rights Holder: 東京医科歯科大学・JST
  • Filing Date: 2006-04-26
  • Overseas
• [Patent(Industrial Property Rights)] PSYCHOGENIC PAIN THERAPEUTIC AGENT (2006)
  • Inventor(s): 田邊勉
  • Industrial Property Rights Holder: 東京医科歯科大学・JST
  • Filing Date: 2006-02-10
  • Overseas
• [Patent(Industrial Property Rights)] REMEDY FOR NEUROGENIC PAIN (2006)
  • Inventor(s): 田邊勉
  • Industrial Property Rights Holder: 東京医科歯科大学・JST
  • Filing Date: 2006-02-10
  • Overseas