Novel regulator of gene expression in DRG in a neuropathic pain

• Project/Area Number: 24659688
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Orthopaedic surgery
• Research Institution: Hyogo Medical University
• Principal Investigator: NOGUCHI Koichi 兵庫医科大学, 医学部, 教授 (10212127)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 脊髄神経節 / 遺伝子発現 / Artemin / TRPV1 / TRPA1 / 神経障害性疼痛 / 炎症性疼痛 / 後根神経節 / DRG / 痛覚過敏

Research Abstract

We found the following findings. 1. Artemin increases locally in skin over long periods of time, whereas NGF shows transient increases after peripheral inflammation. 2. Artemin increases in peripheral sciatic nerve following to the Wallerian degeneration after nerve injury. 3. Repeated artemin injections changed the gene expressions of TRPV1 and TRPA1 in DRG neurons. 4. The co-localization between TRPV1/A1 and GFRalpha3 was higher than that between TRPV1/A1 and TrkA. 5. Continuous artemin injection into the plantar surface caused mechanical and heat hyperalgesia. 6. Artemin increases TRPV1/A1 expression and Ca activity in primary cultured DRG neurons. 7. TRPV1/A1 expression was regulated by artemin through p38 phosphorylation in primary afferent.
We conclude that peripheral tissue-derived artemin synthesis is important regulator of TRPV1/A1 expression in DRG neurons following peripheral inflammation and nerve injury.

Research Products

• [Journal Article] Etodolac activates and desensitizes transient receptor potential ankyrin 1 (TRPA1) (2013)
  • Author(s): Shenglan Wang, Yi Dai, Yoko Kogure, Satoshi Yamamoto, Wensheng Zhang, Koichi Noguchi
  • Journal Title: J. Neurosci. Res Volume: 91 Pages: 1591-98
  • Peer Reviewed
• [Journal Article] Transient receptor potential channel A1 involved in calcitonin gene-related peptide release in neurons (2013)
  • Author(s): Nobumasa Usio, Yi Dai, Shenglan Wang, Tetsuo Fukuoka, Koichi Noguchi
  • Journal Title: Neural Regen Res Volume: 8 Pages: 3013-3019
  • Peer Reviewed
• [Journal Article] Upregulated glial cell line-derived neurotrophic factor through cyclooxygenase-2 activation in the muscle is required for mechanical hyperalgesia after exercise in rats (2013)
  • Author(s): Shiori Murase, Etsuji Terazawa, Kenji Hirate, Hiroki Yamanaka, Hirosato Kanda, Koichi Noguchi, Hiroki Ota, Fernando Queme, Toru Taguchi, Kazue Mizumura
  • Journal Title: J. Physiol Volume: 591 Pages: 3035-48
  • Peer Reviewed
• [Journal Article] Activation of p38 MAPK through transient receptor potential A1 in a rat model of gastric distention-induced visceral pain (2013)
  • Author(s): Kondo T, Sakurai J, Miwa H, Noguchi K
  • Journal Title: Neuroreport Volume: 24 Pages: 68-72
  • Peer Reviewed
• [Journal Article] COX-1-dependent prostaglandin D2 in microglia contributes to neuropathic pain via DP2 receptor in spinal neurons (2013)
  • Author(s): Kanda H, Kobayashi K, Yamanaka H, Noguchi K
  • Journal Title: Glia Volume: 61 Pages: 943-56
  • Peer Reviewed
• [Journal Article] Modulation of TRP channels by resveratrol and other stilbenoids (2013)
  • Author(s): Y u L, Wang S, Kogure Y, Yamamoto S, Noguchi K, Dai Y
  • Journal Title: Mol Pain Volume: 9 Pages: 3-3
  • Peer Reviewed
• [Journal Article] Etodolac activates and desensitizes transient receptor potential ankyrin 1 (2013)
  • Author(s): Wang S, Dai Y, Kogure Y, Yamamoto S, Zhang W, Noguchi K
  • Journal Title: J Neurosci Res Volume: 91(12) Issue: 12 Pages: 1591-8
  • DOI: 10.1002/jnr.23274
  • Peer Reviewed
• [Journal Article] Upregulated glial cell line-derived neurotrophic factor through cyclooxygenase-2 activation in the muscle is required for mechanical hyperalgesia after exercise in rats. (2013)
  • Author(s): S. Murase, E. Terazawa, K. Hirate, H. Yamanaka, H. Kanda, K. Noguchi, H. Ota, F. Queme, T. Taguchi, and K. Mizumura.
  • Journal Title: Journal of Physiology Volume: 591 Issue: 12 Pages: 3035-3048
  • DOI: 10.1113/jphysiol.2012.249235
  • Peer Reviewed
• [Journal Article] Activation of p38 MAPK through transient receptor potential A1 in a rat model of gastric distension-induced visceral pain. (2013)
  • Author(s): Kondo T, Sakurai J, Miwa H, Noguchi K.
  • Journal Title: Neuroreport Volume: 24 Issue: 2 Pages: 68-72
  • DOI: 10.1097/wnr.0b013e32835c7df2
  • Peer Reviewed
• [Journal Article] COX-1-dependent prostaglandin D2 in microglia contributes to neuropathic pain via DP2 receptor in spinal neurons. (2013)
  • Author(s): Kanda H, Kobayashi K, Yamanaka H, Noguchi K.
  • Journal Title: Glia Volume: 61 Issue: 6 Pages: 943-956
  • DOI: 10.1002/glia.22487
  • Peer Reviewed
• [Journal Article] Modulation of TRP channels by resveratrol and other stilbenoids. (2013)
  • Author(s): Yu L, Wang S, Kogure Y, Yamamoto S, Noguchi K, Dai Y.
  • Journal Title: Mol Pain. Volume: Vol.9 Pages: 3-13
  • DOI: 10.1186/1744-8069-9-3
  • Peer Reviewed
• [Journal Article] Phosphorylation of Ezrin/Radixin/Moesin(ERM) protein in spinal microglia following peripheral nerve injury and lysophosphatidic acid administration. (2012)
  • Author(s): Kashimoto R, Yamanaka H, Kobayashi K, Okubo M, Yagi H, Mimura O, Noguchi K.
  • Journal Title: Glia Volume: 61 Issue: 3 Pages: 338-48
  • DOI: 10.1002/glia.22436
  • Peer Reviewed
• [Journal Article] Increased expression of interleukin-18 in the trigeminalspinal subnucleus caudalis after inferior alveolar nerve injury in the rat. (2012)
  • Author(s): Daigo E, Sakuma Y, Miyoshi K, Noguchi K, Kotani J.
  • Journal Title: Neurosci Lett Volume: 529 Issue: 1 Pages: 39-44
  • DOI: 10.1016/j.neulet.2012.09.007
  • Peer Reviewed
• [Journal Article] An ultrastructural evidence for the expression of transient receptor potential ankyrin 1 (TRPA1) in astrocytes in the rat trigeminal caudal nucleus (2012)
  • Author(s): Lee SM, Cho YS, Kim TH, Jin MU, Ahn DK, Noguchi K, Bae YC.
  • Journal Title: J Chem Neuroanat Volume: 45 Issue: 1-2 Pages: 45-9
  • DOI: 10.1016/j.jchemneu.2012.07.003
  • Peer Reviewed
• [Journal Article] Noguchi K. Multiple P2Y subtypes in spinal microglia are involved in neuropathic pain after peripheral nerve injury. (2012)
  • Author(s): Kobayashi K, Yamanaka H, Yanamoto F, Okubo M
  • Journal Title: Glia Volume: 60 Issue: 10 Pages: 1529-39
  • DOI: 10.1002/glia.22373
  • Peer Reviewed
• [Journal Article] Potentiation of the P2X3 ATP receptor by PAR-2 in rat DRG neurons, through protein kinase-dependent mechanisms, contributes to inflammatory pain (2012)
  • Author(s): Wang S, Dai Y, Kobayashi K, Zhu W, Kogure Y, Yamanaka H, Wan Y, Zhang W, Noguchi K.
  • Journal Title: Eur J Neurosci Volume: 36 Issue: 3 Pages: 2293-301
  • DOI: 10.1111/j.1460-9568.2012.08142.x
  • Peer Reviewed
• [Journal Article] Up-regulation of platelet-activating factor synthases and its receptor in spinal cord contribute to development of neuropathic pain following peripheral nerve injury. (2012)
  • Author(s): Okubo M, Yamanaka H, Kobayashi K, Kanda H, Dai Y, Noguchi K.
  • Journal Title: Mol Pain Volume: 8 Pages: 8-8
  • DOI: 10.1186/1744-8069-8-8
  • Peer Reviewed
• [Journal Article] Re-evaluation of the phenotypic changes in L4 dorsal root ganglion neurons after L5 spinal nerve ligation (2012)
  • Author(s): Fukuoka T, Yamanaka H, Kobayashi K, Okubo M, Miyoshi K, Dai Y, Noguchi K
  • Journal Title: Pain Volume: 153 Issue: 1 Pages: 68-79
  • DOI: 10.1016/j.pain.2011.09.009
  • Peer Reviewed
• [Presentation] 痛みの分子メカニズムと臨床病態 (2013)
  • Author(s): 野口光一
  • Organizer: 第6回日本運動器疼痛学会
  • Place of Presentation: 神戸
  • Year and Date: 2013-12-07
  • Invited
• [Presentation] 痛みの分子メカニズムと治療 (2013)
  • Author(s): 野口光一
  • Organizer: 西宮労災指定医協会総会
  • Place of Presentation: 芦屋
  • Year and Date: 2013-07-25
• [Presentation] Molecular Mechanism of Pain (2013)
  • Author(s): Noguchi K
  • Organizer: The International Society for the Study of the Lumbar Spine Annual Meeting 2013
  • Place of Presentation: Arizona
  • Year and Date: 2013-05-15
  • Invited
• [Presentation] 痛みの分子メカニズム (2013)
  • Author(s): 野口光一
  • Organizer: 第10回神経因性疼痛研究会
  • Place of Presentation: 神戸
  • Year and Date: 2013-04-19
• [Presentation] 一知覚ニューロンにおけるArteminによる炎症時のTRPV1/A1の発現制御 (2013)
  • Author(s): 野口光一,宮川慈子
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: 横浜(シンポジウム・ワークショップ・パネル(指名))
  • Year and Date: 2013-03-27
• [Presentation] 機能外科のための神経科学 (2013)
  • Author(s): 野口光一
  • Organizer: 第52回日本定位・機能神経外科学会
  • Place of Presentation: 岡山(シンポジウム・ワークショップ・パネル(指名))
  • Year and Date: 2013-01-19
• [Presentation] Molecular Mechanism of Pain. (2013)
  • Author(s): Noguchi K.
  • Organizer: The International Society for the Study of the Lumbar Spine Annual Meeting
  • Place of Presentation: Arizona, U.S.A
  • Invited
• [Presentation] Leukotriene enhances NMDA induced inward currents in dorsal horn neurons of rat spinal cord after peripheral nerve injury. (2013)
  • Author(s): Kiyoyuki Y, Yamanaka H, Kobayashi K, Okubo M, Noguchi K, Taniguchi W, Nishio N, Nakatsuka T.
  • Organizer: The 43nd Annual Meeting of the Society for Neuroscience
  • Place of Presentation: San Diego, U.S.A
• [Presentation] Expression of colony-stimulateing factors and their receptors in dorsal root ganglion and spinal cord after peripheral nerve injury. (2013)
  • Author(s): Okubo M, Yamanaka H, Kobayashi K, Kanda H, Dai Y, Noguchi K.
  • Organizer: The 43nd Annual Meeting of the Society for Neuroscience
  • Place of Presentation: San Diego, U.S.A
• [Presentation] 痛みの分子メカニズムと臨床病態 (2013)
  • Author(s): 野口光一
  • Organizer: 第６回日本運動器疼痛学会
  • Place of Presentation: 神戸
  • Invited
• [Presentation] 侵害受容系の変化と神経障害性疼痛のメカニズム. (2013)
  • Author(s): 野口光一
  • Organizer: 第42回日本脊椎脊髄病学会
  • Place of Presentation: 宜野湾
  • Invited
• [Presentation] 神経障害性疼痛の動物モデルと遺伝子発現 (2012)
  • Author(s): 野口光一
  • Organizer: 第27回日本整形外科学会基礎学術集会
  • Place of Presentation: 名古屋(シンポジウム)
  • Year and Date: 2012-10-27
  • Invited
• [Presentation] 痛み研究の目指すところ : 今後の研究の方向性について (2012)
  • Author(s): 野口光一
  • Organizer: 日本ペインクリニック学会第46回大会
  • Place of Presentation: 出雲(シンポジウム)
  • Year and Date: 2012-07-06
• [Presentation] 痛みの科学?神経障害性疼痛のメカニズムと神経可塑性? (2012)
  • Author(s): 野口光一
  • Organizer: 日本ペインクリニック学会第46回大会
  • Place of Presentation: 出雲(共催セミナー)
  • Year and Date: 2012-07-05
• [Presentation] Leukotriene synthases and the receptors in nociceptive pathway contribute to the neuropathic and inflammatory pain (2012)
  • Author(s): Noguchi K
  • Organizer: 4th World Cogress on Pain (IASP 2012)
  • Place of Presentation: Milan
• [Book] 痛みのScience and Practice (2013)
  • Author(s): 宮川慈子,野口光一
  • Publisher: 文光堂