Molecular mechanisms of neuropathic pain

2009 Fiscal Year Final Research Report

• Project/Area Number: 19300121
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Hyogo College of Medicine
• Principal Investigator: NOGUCHI Koichi Hyogo College of Medicine, 医学部, 教授 (10212127)
• Project Period (FY): 2007 – 2009
• Keywords: 後根神経節 / MAPキナーゼ / 脊髄後角 / ATP受容体 / 疼痛行動 / 神経障害

Research Abstract

In order to examine the novel mechanism of neuropathic pain, we have used the rat model of neuropathic pain and explored the expression and the role of several molecules in nociceptive pathway. As a result, we have found that some intracellular signaling molecules, ATP receptors and some cytokines have important roles in dorsal root ganglion neurons, spinal dorsal horn neurons and spinal glial cells. These results were published in international high-level journals. We believe that these findings are expected as novel seeds for development of new therapeutic drug of neuropathic pain.

Research Products

• [Journal Article] Expression of transient receptor potential ankyrin 1 (TRPA1) in the rat trigeminal sensory afferents and spinal dorsal horn (2010)
  • Author(s): Kim YS, Son JY, Kim TH, Paik SK, Dai Y, Noguchi K, Ahn DK, Bae YC
  • Journal Title: J Comp Neurol 518 Pages: 687-98
  • Peer Reviewed
• [Journal Article] Leukotriene synthases and the receptors induced by peripheral nerve injury in the spinal cord contribute to the generation of neuropathic pain (2010)
  • Author(s): Okubo M, Yamanaka H, Kobayashi K, Noguchi K
  • Journal Title: Glia 58 Pages: 599-610
  • Peer Reviewed
• [Journal Article] Transient receptor potential A1 mediates gastric distention-induced visceral pain in rats (2009)
  • Author(s): Kondo T, Obata K, Miyoshi K, Sakurai J, Tanaka J, Miwa H, Noguchi K
  • Journal Title: Gut 58 Pages: 1342-52
  • Peer Reviewed
• [Journal Article] Differential activation of p38 and extracellular signal-regulated kinase in spinal cord in a model of bee venom-induced inflammation and hyperalgesia (2008)
  • Author(s): Cui, X.Y., Dai, Y., Wang, S.L., Yamanaka, H., Kobayashi, K., Obata, K., Chen, J., Noguchi, K
  • Journal Title: Mol. Pain 4 Pages: 17
  • Peer Reviewed
• [Journal Article] Activation of extracellular signal-regulated protein kinase in sensory neurons after noxious gastric distention and its involvement in acute visceral pain in rats (2008)
  • Author(s): Sakurai, J., Obata, K., Ozaki, N., Tokunaga, A., Kobayashi, K., Yamanaka, H., Dai, Y., Kondo, T., Miyoshi, K., Sugiura, Y., Matsumoto, T., Miwa, H., Noguchi, K
  • Journal Title: Gastroenterology 134 Pages: 1094-1103
  • 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., Noguchi, K
  • Journal Title: Brain 131 Pages: 1241-1251
  • 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., Noguchi, K
  • Journal Title: J. Neurosci 28 Pages: 2892-2902
  • 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., Noguchi, K
  • Journal Title: Glia 56 Pages: 723-733
  • 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., Kobayashi, K., Yamanaka, H., Obata, K., Dai, Y., Noguchi, K
  • Journal Title: J. Comp. Neurol 510 Pages: 188-206
  • Peer Reviewed
• [Journal Article] Interleukin-18-mediated microglia/astrocyte interaction in the spinal cord enhances neuropathic pain processing after nerve injury (2008)
  • Author(s): Miyoshi, K., Obata, K., Kondo, T., Okamura, H., Noguchi, K
  • Journal Title: J. Neurosci 28 Pages: 12775-12787
  • Peer Reviewed
• [Journal Article] Axotomy increases plasma membrane Ca2+ pump isoform4 in primary afferent neurons (2007)
  • Author(s): Ogura, H., Tachibana, T., Yamanaka, H., Kobayashi, K., Obata, K., Dai, Y., Yoshiya, S., Noguchi, K
  • Journal Title: Neuroreport 18 Pages: 17-22
  • Peer Reviewed
• [Journal Article] Alternation of the cell adhesion molecule L1 expression in a specific subset of primary afferent neurons contributes to neuropathic pain (2007)
  • Author(s): Yamanaka, H., Obata, K., Kobayashi, K., Dai, Y., Fukuoka, T., Noguchi, K
  • Journal Title: Eur. J. Neurosci 25 Pages: 1097-1111
  • Peer Reviewed
• [Journal Article] Tissue type plasminogen activator induced in rat dorsal horn astrocytes contributes to mechanical hypersensitivity following dorsal root injury (2007)
  • Author(s): Kozai, T., Yamanaka, H., Dai, Y., Obata, K., Kobayashi, K., Mashimo, T., Noguchi, K
  • Journal Title: Glia 55 Pages: 595-603
  • 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., Obata, K., Katsura, H., Sakurai, J., Kobayashi, K., Yamanaka, H., Dai, Y., Fukuoka, T., Mashimo, T., Noguchi, K
  • Journal Title: J. Pharmacol. Exp. Ther 321 Pages: 28-34
  • 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., Katsura, H., Mizushima, T., Sakurai, J., Kobayashi, K., Yamanaka, H., Dai, Y., Fukuoka, T., Noguchi, K
  • Journal Title: J. Neurochem 102 Pages: 1569-1584
  • 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., Noguchi, K
  • Journal Title: J. Neurochem 102 Pages: 1614-1624
  • Peer Reviewed
• [Journal Article] Frequency-dependent ERK phosphorylation in spinal neurons by electric stimulation of the sciatic nerve and the role in electrophysiological activity (2007)
  • Author(s): Fukui, T., Dai, Y., Iwata, K., Kamo, H., Yamanaka, H., Obata, K., Kobayashi, K., Wang, S., Cui, X., Yoshiya, S., Noguchi, K
  • Journal Title: Mol. Pain 3 Pages: 18
  • 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., 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
  • Author(s): Yamanaka, H., Obata, K., Kobayashi, K., Dai, Y., Fukuoka, T., Noguchi, K
  • Journal Title: Neuroscience Pages: 202-21
  • Peer Reviewed
• [Presentation] Platelet-activating factor biosynthesis in spinal cord contributes to neuropathic pain following peripheral nerve injury (2009)
  • Author(s): Okubo M, Yamanaka, H., Kobayashi K, Noguchi K
  • Organizer: The 39th Annual Meeting of the Society for Neuroscience (Neuroscience 2009)
  • Place of Presentation: Chicago, U.S.A
  • Year and Date: 20091017-20091021
• [Presentation] 痛みの分子メカニズム (2009)
  • Author(s): 野口光一
  • Organizer: 第31回日本疼痛学会
  • Place of Presentation: 名古屋
  • Year and Date: 20090717-20090718
• [Presentation] 脊髄後角における痛覚伝達の分子メカニズム (2009)
  • Author(s): 野口光一
  • Organizer: 第19回神経科学の基礎と臨床
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-19
• [Presentation] 痛みの分子メカニズム (2009)
  • Author(s): 野口光一
  • Organizer: 第11回Macnab Memorial Lecture
  • Place of Presentation: 福島
  • Year and Date: 2009-12-05
• [Presentation] 炎症性疼痛の分子メカニズム (2009)
  • Author(s): 野口光一
  • Organizer: 第1回日本線維筋痛症学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-10-11
• [Presentation] 痛み-その発生機序と臨床的制御の意義-「炎症性疼痛の分子メカニズム」 (2009)
  • Author(s): 野口光一
  • Organizer: 第53回日本リウマチ学会総会.学術集会(JCR 2009)
  • Place of Presentation: 東京
  • Year and Date: 2009-04-24
• [Presentation] Induction of annexin A2 in rat dorsal root ganglia and spinal cord following peripheral nerve injury. (2008)
  • Author(s): Yamanaka, H., Okubo, M., Kobayashi, K., Noguchi, K
  • Organizer: The 38th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Washington D.C., U.S.A
  • Year and Date: 20081115-20081119
• [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., Noguchi, K
  • Organizer: The 38th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Washington D.C., U.S.A
  • Year and Date: 20081115-20081119
• [Presentation] Upregulation of leukotriene synthesis in glial cells contributes to neuropathic pain following peripheral nerve injury (2008)
  • Author(s): Okubo, M., Yamanaka, H., Kobayashi, K., Noguchi, K
  • Organizer: The 38th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Washington D.C., U.S.A
  • Year and Date: 20081115-20081119
• [Presentation] MAP kinase regulation of pain: peripheral, central and glial mechanisms (2008)
  • Author(s): Noguchi, K
  • Organizer: (Workshops) 12th World Congress on Pain
  • Place of Presentation: Glasgow, U.K
  • Year and Date: 20080817-20080822
• [Presentation] TRP channels and nociception (2008)
  • Author(s): Noguchi, K
  • Organizer: (Workshops) 12th World Congress on Pain
  • Place of Presentation: Glasgow, U.K
  • Year and Date: 20080817-20080822
• [Presentation] Neuropathic pain mechanisms: TRP family and signal transduction molecules (2008)
  • Author(s): Noguchi, K
  • Organizer: (Plenary Lecture) NeuPSIG satellite to the Glasgow 2008 World Congress on Pain
  • Place of Presentation: London, U.K
  • Year and Date: 20080813-20080815
• [Presentation] Contribution of changes in signal transduction molecules in DRG and spinal cord to neuropathic pain (2008)
  • Author(s): Noguchi, K
  • Organizer: (Symposium) The 3rd Asian Pain Symposium
  • Place of Presentation: Fukuoka
  • Year and Date: 20080718-20080719
• [Presentation] 痛みのメカニズム-最近のトピックス-. (2008)
  • Author(s): 野口光一
  • Organizer: 特別講演)第22回日本歯科麻酔学会リフレッシャーコース
  • Place of Presentation: 東京
  • Year and Date: 2008-07-13
• [Presentation] 痛み伝達の調節機構-trpファミリー分子とシグナル伝達-(特別講演) (2008)
  • Author(s): 野口光一
  • Organizer: 第22回日本ニューロモデュレーション学会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-18
• [Presentation] 分子と痛み(1):シグナルと痛み-MAPKを中心として (2007)
  • Author(s): 野口光一
  • Organizer: (特別講演)第2回痛み研究者の集い
  • Place of Presentation: 京都
  • Year and Date: 20071006-20071007
• [Presentation] Roles of ERK5 in spinal microglia and primary sensory neurons for neuropathic pain (2007)
  • Author(s): Noguchi, K
  • Organizer: Symposium) 7th IBRO World Congress of Neuroscience
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 20070712-20070717
• [Presentation] Roles of extracellular signal-regulated protein kinase (ERK)5 in spinal microglia and primary sensory neurons for neuropathic pain (2007)
  • Author(s): Noguchi, K
  • Organizer: (Workshop) Second International Congress on Neuropathic Pain
  • Place of Presentation: Berlin, Germany
  • Year and Date: 20070607-20070610
• [Presentation] 疼痛伝達の分子メカニズムの解明. (指定講演)次世代の神経科学研究 (2007)
  • Author(s): 野口光一
  • Organizer: 第313回大阪大学神経科学懇話会
  • Place of Presentation: 大阪
  • Year and Date: 2007-12-22
• [Presentation] TRP channel family and cutaneous sensation (2007)
  • Author(s): 野口光一
  • Organizer: 指定講演)第17回国際痒みシンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2007-09-15
• [Book] 痛みのメカニズム. 運動器の痛み診療ハンドブック (2007)
  • Author(s): 小畑浩一, 野口光一
  • Total Pages: 2-17
  • Publisher: 南江堂
• [Book] Encyclopedic Reference of Pain, 1st ed(Regulation of ERK in sensory neurons during inflammation) (2007)
  • Author(s): Obata, K., Dai, Y., Noguchi, K
  • Publisher: Springer-Verlag