Comparative study of the expression of voltage-gated ion channel mRNAs in a rat neuropathic pain model

• Project/Area Number: 19603019
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pain science
• Research Institution: Hyogo College of Medicine
• Principal Investigator: FUKUOKA Tetsuo Hyogo College of Medicine, 医学部, 非常勤講師 (90399147)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI Kimiko 兵庫医科大学, 医学部, 助教 (70418961)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2007: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: DRG / Nav / Kv / 腰部交感神経節 / 脊髄 / 神経因性疼痛 / DRG(後根神経節) / Nav(電位依存型ナトリウムチャネル) / Kv(電位依存型カリウムチャネル)

Research Abstract

局所麻酔薬は、神経の電位依存性ナトリウムチャネル(Nav)に働いて、痛みの伝達をブロックする。Nav には1.1 から1.9 迄の9 つがある。より選択的で副作用の少ない局所麻酔薬開発の基礎研究として、知覚神経系におけるこれらの遺伝子の分布の違いを個々の細胞レベルで明らかにし、病態に応じた局所麻酔薬のターゲット分子として、Nav1.3, 1.7, 1.8, 1.9が重要であることを見いだした。

Research Products

• [Journal Article] Comparative study of the distribution of the alpha-subunits of voltage-gated sodium channels in normal and axotomized rat dorsal root ganglion neurons. (2008)
  • Author(s): Fukuoka, T., Kobayashi, K., Yamanaka, H., Obata, K., Dai, Y. and Noguchi, K.
  • Journal Title: J. Comp. Neurol. 10, 510 Pages: 188-206
  • Peer Reviewed
• [Journal Article] Transforming growth factor-activated kinase 1 induced in spinal astrocytes contributes to mechanical hypersensitivity after nerve injury. (2008)
  • Author(s): Katsura, H., Obata, K., Miyoshi, K., Kondo, T., Yamanaka, H., Kobayashi, K., Dai, Y., Fukuoka, T., Sakagami, M. and Noguchi, K.
  • Journal Title: Glia 56 Pages: 723-733
  • Peer Reviewed
• [Journal Article] P2Y12 receptor upregulation in activated microglia is a gateway of p38 signaling and neuropathic pain (2008)
  • Author(s): Kobayashi, K., Yamanaka, H., Fukuoka, T., Dai, Y., Obata, K. and Noguchi, K.
  • Journal Title: J. Neurosci. 12, 28 Pages: 2892-902
  • Peer Reviewed
• [Journal Article] Phospholipase C and protein kinase A mediate bradykinin sensitization of TRPA1 : a molecular mechanism of inflammatory pain (2008)
  • Author(s): Wang, S., Dai, Y., Fukuoka, T., Yamanaka, H., Kobayashi, K., Obata, K., Cui, X., Tominaga, M. and Noguchi, K.
  • Journal Title: Brain. 131(Pt-5) Pages: 1241-1251
  • Peer Reviewed
• [Journal Article] Toll-like receptor 3 contributes to spinal glial activation and tactile allodynia after nerve injury. (2008)
  • Author(s): Obata, K., Katsura, H., Miyoshi, K., Kondo, T., Yamanaka, H., Kobayashi, K., Dai, Y., Fukuoka, T., Akira, S. and Noguchi K.
  • Journal Title: J. Neurochem. 105 Pages: 2249-2259
  • Peer Reviewed
• [Journal Article] Comparative study of the distribution of the alpha-subunits of voltage-gated sodium channels in normal and axotomized rat dorsal root ganglion neurons. (2008)
  • Author(s): Fukuoka, T., et. al.
  • Journal Title: J. Comp. Neurol. 510 Pages: 188-206
  • Peer Reviewed
• [Journal Article] Transforming growth factor-activated kinase 1 induced in spinal astrocytes contributes to mechanical hypersensitivity after nerve injury. (2008)
  • Author(s): Katsura, H., et. al.
  • Journal Title: Glia 56 Pages: 723-733
  • Peer Reviewed
• [Journal Article] P2Y12 receptor upregulation in activated microglia is a gateway of p38 signaling and neuropathic pain. (2008)
  • Author(s): Kobayashi, K. et. al.
  • Journal Title: J. Neurosci. 28 Pages: 2892-2902
  • Peer Reviewed
• [Journal Article] Phospholipase C and protein kinase A mediate bradykinin sensitization of TRPA1 : a molecular mechanism of inflammatory pain. (2008)
  • Author(s): Wang, S., et. al.
  • Journal Title: Brain 131 Pages: 1241-1251
  • Peer Reviewed
• [Journal Article] Toll-like receptor 3 contributes to spinal glial activation and tactile allodynia after nerve injury. (2008)
  • Author(s): Obata, K. et. al.
  • Journal Title: J. Neurochem. 105 Pages: 2249-2259
  • Peer Reviewed
• [Journal Article] Transforming growth factor-activated kinase 1 induced in spinal astrocytes contributes to mechanical hypersensitivity after nerve injury (2008)
  • Author(s): Katsura, H., et. al.
  • Journal Title: Glia (In press)
  • Peer Reviewed
• [Journal Article] P2Y12 receptor upregulation in activated microglia is a gateway of p38 signaling and neuropathic pain (2008)
  • Author(s): Kobayashi, K., et. al.
  • Journal Title: J.Neurosci. 28 Pages: 2892-2902
  • Peer Reviewed
• [Journal Article] Phospholipase C and protein kinase A mediate bradykinin sensitization of TRPA1:a molecular mechanism of inflammatory pain (2008)
  • Author(s): Wang, S., et. al.
  • Journal Title: Brain (In press)
  • Peer Reviewed
• [Journal Article] Sensitization of TRPA1 by PAR2 contributes to the sensation of inflammatory pain. (2007)
  • Author(s): Dai, Y., Wang, S., Tominaga, M., Yamamoto, S., Fukuoka, T., Higashi, T., Kobayashi, K., Obata, K., Yamanaka, H. and Noguchi, K.
  • Journal Title: J. Clin. Invest. 117 Pages: 1979-1987
  • Peer Reviewed
• [Journal Article] Activation of fibroblast growth factor receptor by axotomy, through downstream p38 in dorsal root ganglion, contributes to neuropathic pain. (2007)
  • Author(s): Yamanaka, H., Obata, K., Kobayashi, K., Dai, Y., Fukuoka, T. and Noguchi, K.
  • Journal Title: Neuroscience 150 Pages: 202-211
  • Peer Reviewed
• [Journal Article] Activation of extracellular signal-regulated protein kinases 5 in primary afferent neurons contributes to heat and cold hyperalgesia after inflammation. (2007)
  • Author(s): Katsura, H., Obata, K., Mizushima, T., Sakurai, J., Kobayashi, K., Yamanaka, H., Dai, Y., Fukuoka, T., Sakagami, M. and Noguchi, K.
  • Journal Title: J. Neurochem. 102 Pages: 1614-1624
  • Peer Reviewed
• [Journal Article] Intensity-dependent activation of extracellular signal-regulated protein kinases 5 in sensory neurons contributes to pain hypersensitivity (2007)
  • Author(s): Mizushima, T., et. al.
  • Journal Title: J.Pharmacol.Exp.Ther. 321 Pages: 28-34
  • Peer Reviewed
• [Journal Article] Sensitization of TRPA1 by PAR2 contributes to the sensation of inflammatory pain (2007)
  • Author(s): Dai, Y., et. al.
  • Journal Title: J.Clin.Invest. 117 Pages: 1979-1987
  • Peer Reviewed
• [Journal Article] Activation of extracellular slgnal-regulated protein kinases 5 in primary afferent neurons contributes to heat and cold hyperalgesia after inflammation (2007)
  • Author(s): Katsura, H., et. al.
  • Journal Title: J.Neurochem. 102 Pages: 1614-1624
  • Peer Reviewed
• [Journal Article] Roles of extracellular signal-regulated protein kinases 5 in spinal microglia and primary sensory neurons for neuropathic pain (2007)
  • Author(s): Obata, K., et. al.
  • Journal Title: J.Neurochem. 102 Pages: 1569-1584
  • Peer Reviewed
• [Journal Article] Activation of fibroblast growth factor receptor by axotomy,through downstream p38 in dorsal root ganglion,contributes to neuropathic pain (2007)
  • Author(s): Yamanaka, H., et. al.
  • Journal Title: Neuroscience 150 Pages: 202-211
  • Peer Reviewed
• [Presentation] Laminae-specific distribution of Nav mRNAs in the rat spinal cord. (2008)
  • Author(s): Fukuoka, T., et. al.
  • Organizer: The 38th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Washington D. C.
  • Year and Date: 2008-11-15
• [Presentation] Induction of P2Y receptor in the spinal cord following peripheral nerve injury. (2008)
  • Author(s): Kobayashi, K., Yamanaka, H., Fukuoka, T. and Noguchi, K.
  • Organizer: The 38th Annual Meeting Society for Neuroscience
  • Place of Presentation: Washington, DC., U.S.A.
• [Presentation] Laminae-specific distribution of Nav mRNAs in the rat spinal cord. (2008)
  • Author(s): Fukuoka, T., Kobayashi, K., Yamanaka, H., Obata, K., Dai, Y. and Noguchi, K.
  • Organizer: The 38th Annual Meeting Society for Neuroscience
  • Place of Presentation: Washington, DC., U.S.A.
• [Presentation] 一次知覚ニューロンにおける電位依存性ナトリウムチャネルサブタイプの発現比較 (2008)
  • Author(s): 福岡哲男, 小林希実子, 山中博樹, 戴毅, 小畑浩一, 野口光一
  • Organizer: 第30回日本疼痛学会
  • Place of Presentation: 福岡
• [Presentation] Protease-activated receptor2によるTRPA1活性の増強 (2007)
  • Author(s): 戴毅, 王勝蘭, 福岡哲男, 富永真琴, 野口光一
  • Organizer: 第29回日本疼痛学会,
  • Place of Presentation: 横浜
  • Year and Date: 2007-07-07
• [Presentation] 神経因性疼痛における脊髄マイクログリアに発現するP2Y12受容体の関与 (2007)
  • Author(s): 小林希実子, 福岡哲男, 山中博樹, 野口光一
  • Organizer: 第29回日本疼痛学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-07-07
• [Presentation] BradykininによるTRPA1活性の増強 (2007)
  • Author(s): 王勝蘭, 戴毅, 福岡哲男, 富永真琴, 野口光一
  • Organizer: 第29回日本疼痛学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-07-07
• [Presentation] P2Y12 receptor expressed in spinal microglia contributes to neuropathic pain. (2007)
  • Author(s): Kobayashi, K., Fukuoka, T., Yamanaka, H. and Noguchi, K.
  • Organizer: 37th Annual Meeting Society for Neuroscience
  • Place of Presentation: San Diego, U.S.A.
• [Presentation] 神経因性疼痛における脊髄マイクログリアに発現するP2Y12 受容体の関与. (2007)
  • Author(s): 小林希実子, 福岡哲男, 山中博樹, 野口光一
  • Organizer: 第30回日本神経科学大会
  • Place of Presentation: 横浜
• [Presentation] P2Y12 receptor expressed in spinal microglia contributes to neuropathic pain (2007)
  • Author(s): Kobayashi, K, et. al.
  • Organizer: 37th Annual Meeting Society for Neuroscience
  • Place of Presentation: San Diego
• [Presentation] Sensitization of TRPA1 by PAR-2 through PLC/PIP2-dependent mechanisms contributes to inflammatory pain (2007)
  • Author(s): Dai, Y., et. al.
  • Organizer: 37th Annual Meeting Society for Neuroscience
  • Place of Presentation: San Diego
• [Presentation] 神経因性疼痛における脊髄マイクログリアに発現するP2Y12受容体の関与 (2007)
  • Author(s): 小林 希実子
  • Organizer: 第30回日本神経科学大会
  • Place of Presentation: 横浜