Epigenetic regulation and central sensitization of neuropathic pain exacerbation under chronic stress condition

• Project/Area Number: 15K21410
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Social dentistry; Pain science
• Research Institution: Nihon University
• Principal Investigator: KATAGIRI Ayano 日本大学, 歯学部, 助教 (40731899)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 神経障害性疼痛 / 神経‐グリア機能連関 / 慢性ストレス / カルシトニン遺伝子関連ペプチド / リン酸化細胞外シグナル調節キナーゼ / ATP受容体 / プロジェクションニューロン / 三叉神経 / サテライトグリア / 末梢感作 / 中枢感作 / エピジェネティック制御 / 三叉神経節 / サテライトグリア細胞

Outline of Final Research Achievements

The aim of this study was to elucidate the peripheral and central nervous mechanisms underlying neuropathic tongue pain and chronic stress. The present findings suggest that calcitonin gene-related peptide (CGRP) released from trigeminal ganglion (TG) neurons activates satellite glial cells (SGCs) through extracellular signal-regulated kinase phosphorylation, resulting in the enhancement of TG neuronal excitability under tongue neuropathic pain. The phenotypic switching of large TG neurons expressing CGRP may account for persistent tongue pain. The functional interaction between SGCs activation via P2Y12R and TG neurons expressing CGRP is a significant contributor to cause neuropathic tongue pain. Our data also suggest that the change in TRPV1 expression via an alteration of epigenetic regulation under the chronic stress or neuropathic pain may cause central sensitization of trigeminal spinal subnucleus caudalis neurons resulting in the exacerbation of tongue neuropathic pain.

Research Products

• [Int'l Joint Research] University of Minnesota(米国)
• [Journal Article] Ascending projections of nociceptive neurons from trigeminal subnucleus caudalis: A population approach. (2017)
  • Author(s): Saito H, Katagiri A, Okada S, Mikuzuki L, Kubo A, Suzuki T, Ohara K, Lee J, Gionhaku N, Iinuma T, Bereiter DA, Iwata K.
  • Journal Title: Experimantal Neurology Volume: 293 Pages: 124-136
  • DOI: 10.1016/j.expneurol.2017.03.024
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 『世界のトップを走る日本のドライアイ最前線』 感覚異常の動物モデルと行動学的評価法 (2017)
  • Author(s): 片桐綾乃，岡田真治，美久月瑠宇，岩田幸一．
  • Journal Title: あたらしい眼科 Volume: Vol. 34 No. 3 Pages: 335-339
• [Journal Article] Oxytocin alleviates orofacial mechanical hypersensitivity associated with infraorbital nerve injury via vasopressin 1A receptors of the rat trigeminal ganglia. (2017)
  • Author(s): Kubo A, Shinoda M, Katagiri A, Takeda M, Suzuki T, Asaka J, Yeomans D, Iwata K.
  • Journal Title: Pain Volume: 158(4) Issue: 4 Pages: 649-659
  • DOI: 10.1097/j.pain.0000000000000808
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Satellite glial cell activation in lingual neuropathic pain via extracellular signal-regulated kinase phosphorylation is associated with phenotypic change in trigeminal ganglion neurons. (2016)
  • Author(s): Ayano Katagiri, Shinji Okada, Hiroto Saito, Lou Mikuzuki, Masamichi Shinoda, Akira Toyofuku and Koichi Iwata
  • Organizer: International Association for the Study of Pain
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2016-09-28
  • Int'l Joint Research
• [Presentation] ERK phosphorylation in medulla and upper cervical cord neurons projecting to thalamus and parabrachial nucleus in rats (2016)
  • Author(s): Hiroto Saito, Ayano Katagiri, Nobuhito Gionhaku and Koichi Iwata
  • Organizer: 16th International Association for the Study of Pain
  • Place of Presentation: パシィフィコ横浜 （神奈川県横浜市）
  • Year and Date: 2016-09-26
  • Int'l Joint Research
• [Presentation] 舌痛発症の末梢神経機構 Neuron-glia interaction in trigeminal ganglion for tangue pain. (2016)
  • Author(s): 片桐 綾乃、 岩田 幸一
  • Organizer: 第21回 日本口腔顔面痛学会
  • Place of Presentation: 神奈川県歯科医師会 （神奈川県横浜市）
  • Year and Date: 2016-09-24
  • Invited
• [Presentation] 三叉神経脊髄路核および上部頸髄投射ニューロンにおけるExtracellular Signal-regulated Kinaseのリン酸化およびNeurokinin 1発現 (2016)
  • Author(s): 岡田 真治、 斎藤 弘人、 片桐 綾乃、 岩田 幸一
  • Organizer: 第21回 日本口腔顔面痛学会
  • Place of Presentation: 神奈川県歯科医師会 （神奈川県横浜市）
  • Year and Date: 2016-09-24
• [Presentation] 舌神経損傷後痛に対する三叉神経節CGRP陽性細胞の表現型変化と神経‐グリア機能連関の関与 (2016)
  • Author(s): 美久月 瑠宇、 片桐 綾乃、 豊福 明、 岩田 幸一
  • Organizer: 第21回 日本口腔顔面痛学会
  • Place of Presentation: 神奈川県歯科医師会 （神奈川県横浜市）
  • Year and Date: 2016-09-24
• [Presentation] ERK phosphorylation of thalamic and parabrachial projection neurons in medulla and upper cervical cord is involved in orofacial nociception in rats (2016)
  • Author(s): Ayano Katagiri , Hiroto Saito and Koichi Iwata
  • Organizer: 第39回 日本神経科学大会
  • Place of Presentation: パシィフィコ横浜 （神奈川県横浜市）
  • Year and Date: 2016-07-20
• [Presentation] Satellite glial cell activation via extracellular signal-regulated kinase phosphorylation, associated with phenotypic change in trigeminal ganglion neurons, is involved in lingual neuropathic pain. (2015)
  • Author(s): Ayano Katagiri, Hiroto Saito, Kinuyo Ohara, Masamichi Shinoda, Akira Toyofuku and Koichi Iwata
  • Organizer: Society for Neuroscience
  • Place of Presentation: Chicago, US
  • Year and Date: 2015-10-17
  • Int'l Joint Research