A cell adhesion molecule close homologue of L1 increased in primary afferent terminal contributes to the development and maintenance of neuropathic pain

• Project/Area Number: 20790170
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Hyogo College of Medicine
• Principal Investigator: YAMANAKA Hiroki Hyogo College of Medicine, 医学部, 講師 (20340995)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 神経因性疼痛 / 細胞間接着 / 脊髄後角 / シナプス / 形態変化 / 細胞間接着因子 / CHL1 / シナプス可塑性 / L1-CAM

Research Abstract

The L1 family of cell adhesion molecules (L1-CAMs) is known to regulate various neural functions that are pivotal to nervous system, including cell adhesion, axon guidance and synaptic plasticity. We investigated the involvement of a close homologue of the L1 cell adhesion molecule (CHL1) on neuropathic pain produced in the rat spared nerve injury (SNI) model. SNI induced the expression of CHL1 in L4/5 DRG neurons, particularly in small size injured neurons and in satellite cells. In the spinal cord, CHL1-immunoreactivity increased in laminae I-II of the dorsal horn ipsilateral to the injury. Ultrastructural study clarified the localization of CHL1 in the axon of primary afferents in the ipsilateral dorsal horn. CHL1 immunoreactivites were localized in the adherence such as axon- axon, axon-dorsal horn neurons (dendrite, soma) and axon-glia (astrocyte and microglia). Experimental inhibition of CHL1 adhesion by chronic intrathecal administration of the anti-CHL1 extracellular domain significantly prevented andreversed SNI-induced mechanical allodynia. Thus, alterations of CHL1 may be involved in the structural plasticity that is associated with neuropathic pain.

Research Products

• [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, et.al.
  • Journal Title: Glia 58 Pages: 599-610
  • 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] 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] 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] 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] 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] 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: 17-17
  • Peer Reviewed
• [Journal Article] Interleukin-18-mediated microglia/astrocyte interaction in the spinalcord enhances neuropathic pain processing after nerve injury (2008)
  • Author(s): Miyoshi, K., et.al.
  • Journal Title: J. Neurosci 28 Pages: 12775-12787
  • 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 nerveinjury (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] 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., et.al.
  • Journal Title: Gastroenterology 134 Pages: 1094-1103
  • 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., et.al.
  • Journal Title: Mol. Pain Pages: 4-17
  • Peer Reviewed
• [Presentation] 末梢神経損傷後に脊髄で増加するP2Y受容体 (2009)
  • Author(s): 小林希実子, 山中博樹, 野口光一
  • Organizer: 第47回日本生物物理学会
  • Place of Presentation: 徳島
  • Year and Date: 2009-11-01
• [Presentation] Transient expression of TNF alpha in the rat spinal cord following peripheral nerve iujury (2009)
  • Author(s): 小林希実子, et.al.
  • Organizer: The 39th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Chicago
  • Year and Date: 2009-10-20
• [Presentation] ラット坐骨神経障害モデルにおけるERMの発現とリン酸化 (2009)
  • Author(s): 樫本良亮, 山中博樹, 小林希実子, 大久保正道, 三村治, 野口光一
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-09-18
• [Presentation] 末梢神経損傷後に脊髄で合成が増加した血小板活性化因子は神経因性疼痛に関与する (2009)
  • Author(s): 大久保正道, 山中博樹, 小林希実子, 野口光一
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-09-18
• [Presentation] 末梢神経損傷後の脊髄後角マイクログリアで増加するp2受容体 (2009)
  • Author(s): 小林希実子, 山中博樹, 大久保正道, 野口光一
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-09-18
• [Presentation] 末梢神経損傷後の脊髄後角マイクログリアで増加するP2受容体 (2009)
  • Author(s): 小林希実子, 他3名
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-09-18
• [Presentation] 末梢神経損傷後に脊髄マイクログリアで増加するP2Y受容体 (2009)
  • Author(s): 小林希実子, 他3名
  • Organizer: 第31回日本疼痛学会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-07-17
• [Presentation] Transient expression of TNF alpha in the rat spinal cord following peripheral nerve iujury. (2009)
  • Author(s): Kobayashi K, Yamanaka, H., Okubo M, Dai Y, Noguchi K.
  • Organizer: The 39th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Chicago, U.S.A.
• [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
  • Place of Presentation: Chicago, U.S.A.
• [Presentation] 末梢神経損傷後に脊髄で増加したロイコトリエンは神経因性疼痛に関与する (2009)
  • Author(s): 大久保正道, 山中博樹, 小林希実子, 野口光一
  • Organizer: 第31回日本疼痛学会
  • Place of Presentation: 名古屋
• [Presentation] 腰部交感神経節ニューロンにおける電位依存性ナトリウムチャネルの発現と軸索切断後の変化 (2009)
  • Author(s): 福岡哲男, 小林希実子, 山中博樹, 野口光一
  • Organizer: 第31回日本疼痛学会
  • Place of Presentation: 名古屋
• [Presentation] 末梢神経損傷後に脊髄マイクログリアで増加するp2y受容体 (2009)
  • Author(s): 小林希実子, 山中博樹, 大久保正道, 野口光一
  • Organizer: 第31回日本疼痛学会
  • Place of Presentation: 名古屋
• [Presentation] Upregulation of leukotriene synthesis in glial cells contributes to neuropathic pain following peripheral nerve injury (2008)
  • Author(s): Okubo, M., et.al.
  • Organizer: The 38th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Washington D. C.
  • Year and Date: 2008-11-18
• [Presentation] Induction of annexin A2 in rat dorsal root ganglia and spinal cord following peripheral nerve iniury (2008)
  • Author(s): Yamanaka, H., et.al.
  • Organizer: The 38th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Washington D. C.
  • Year and Date: 2008-11-17
• [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.
• [Presentation] Induction of P2Y receptor in the spinal cord following peripheral nerve injury (2008)
  • Author(s): Kobayashi, K., Yamanaka, H., Fukuoka, T., Noguchi, K.
  • Organizer: The 38th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Washington D.C., 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., Noguchi, K.
  • Organizer: The 38th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Washington D.C., U.S.A.
• [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.
• [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] 皮膚と後根神経節におけるロイコトリエン合成酵素および受容体の発現 (2008)
  • Author(s): 大久保正道, 山中博樹, 小林希実子, 野口光一
  • Organizer: 第31回日本神経科学大会
  • Place of Presentation: 東京
• [Presentation] ラット後根神経節におけるロイコトリエン受容体の発現 (2008)
  • Author(s): 大久保正道, 山中博樹, 野口光一
  • Organizer: 第57回(社)全日本鍼灸学会学術大会(京都大会)
  • Place of Presentation: 京都