Involvement of glia-neuron functional interaction in intractable trigeminal neuropathic pain

• Project/Area Number: 24659832
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Functional basic dentistry
• Research Institution: Nihon University
• Principal Investigator: IWATA Koichi 日本大学, 歯学部, 教授 (60160115)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI Masayuki 日本大学, 歯学部, 准教授 (00300830) ; NAKANISHI Hiroshi 九州大学, 歯学研究科(研究院), 教授 (20155774) ; SHINODA Masamichi 日本大学, 歯学部, 准教授 (20362238)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 歯科基礎医学 / 神経科学 / 三叉神経 / 疼痛制御 / グリア細胞 / 三叉神経脊髄路核 / 神経障害性疼痛 / 異所性痛覚過敏 / ミクログリア / アストログリア / 神経損傷 / 炎症 / 延髄 / ニューロン-グリア機能連関 / 舌神経 / ATP / P2Y12 / 三叉神経節

Outline of Final Research Achievements

We focused on neuron-glial cell interaction in the trigeminal spinal subnucleus caudalis (Vc) and tried to clarify the mechanisms underlying orofacial extraterritorial pain associated with trigeminal nerve injury or orofacial inflammation. Astroglial and microglial cell activation occurs in the Vc following trigeminal nerve injury or orofacial inflammation via chemokine-immune-cell system and further enhancement of Vc neuronal activity caused by MAP kinase cascade, resulting in the extraterritorial orofacial pain or enhancement of the orofacial motor function.

Research Products

• [Journal Article] Involvement of medullary GABAergic system in extraterritorial neuropathic pain mechanisms associated with inferior alveolar nerve transection (2015)
  • Author(s): Akiko Okada-Ogawa, Yuka Nakaya, Yoshiki Imamura, Masayuki Kobayashi, Masamichi Shinoda, Kozue Kita, Barry J Sessle and Koichi Iwata
  • Journal Title: Exp Neurol Volume: 267 Pages: 42-52
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Involvement of astroglial glutamate-glutamine shuttle in modulation of the jaw-opening reflex following infraorbital nerve injury (2014)
  • Author(s): Rahman Md. Mostafeezur, Hossain Md. Zakir, Masamichi Shinoda, Hanako Takatsuji, Kojiro Takahashi, Yoshiaki Yamada, Kensuke Yamamura, Koichi Iwata and Junichi Kitagawa
  • Journal Title: Eur J Neurosci Volume: 39 Pages: 2050-2059
  • Peer Reviewed / Open Access
• [Journal Article] Morphological and functional changes in regenerated primary afferent fibres following mental and inferior alveolar nerve transection (2014)
  • Author(s): Tsuboi Y, Honda K, Bae YC, Shinoda M, Kondo M, Katagiri A, Echizenya S, Kamakura S, Lee J, Iwata K.
  • Journal Title: Eur J Pain Volume: - Issue: 9 Pages: 1258-1266
  • DOI: 10.1002/ejp.650
  • Peer Reviewed / Open Access
• [Journal Article] Changes in expression of growth-associated protein-43 in trigeminal ganglion neurons and of the jaw opening reflex following inferior alveolar nerve transection in rats. (2013)
  • Author(s): Teramoto K, Tsuboi Y, Shinoda M, Hitomi S, Abe K, Kaji K, Tamagawa T, Suzuki A, Noma N, Kobayashi M, Komiyama O, Urata K, Iwata K.
  • Journal Title: Eur J Oral Sci. Volume: 121 Issue: 2 Pages: 86-91
  • DOI: 10.1111/eos.12021
  • Peer Reviewed / Open Access
• [Journal Article] Nitric oxide signaling contributes to ectopic orofacial neuropathic pain. (2013)
  • Author(s): Sugiyama T, Shinoda M, Watase T, Honda K, Ito R, Kaji K, Urata K, Lee J, Ohara K, Takahashi O, Echizenya S, Iwata K.
  • Journal Title: J Dent Res Volume: 92 Issue: 12 Pages: 1113-1117
  • DOI: 10.1177/0022034513509280
  • Peer Reviewed
• [Journal Article] Involvement of AMPA Receptor GluR2 and GluR3 Trafficking in Trigeminal Spinal Subnucleus Caudalis and C1/C2 Neurons in Acute-Facial Inflammatory Pain. (2012)
  • Author(s): Miyamoto, M.
  • Journal Title: PLoS One Volume: 7 Issue: 8 Pages: e44055-e44055
  • DOI: 10.1371/journal.pone.0044055
  • Peer Reviewed / Open Access
• [Journal Article] ERK is involved in tooth-pressure-induced Fos expression in Vc neurons (2012)
  • Author(s): Hasegawa M, Kondo M* et al.
  • Journal Title: J Dent Res Volume: 91(12) Issue: 12 Pages: 1141-1146
  • DOI: 10.1177/0022034512462397
  • Peer Reviewed / Open Access
• [Journal Article] Satellite glial cell P2Y12 receptor in the trigeminal ganglion is involved in lingual neuropathic pain mechanisms in rats (2012)
  • Author(s): Ayano Katagiri, Masamichi Shinoda, Kuniya Honda, Akira Toyofuku, Barry J Sessle, Koichi Iwata
  • Journal Title: Molecular Pain 2012, 8:23 Volume: 34(4) Pages: 8-23
  • DOI: 10.1186/1744-8069-8-23
  • Peer Reviewed
• [Journal Article] Organization of hyperactive microglial cells in trigeminal spinal subnucleus caudalis and upper cervical spinal cord associated with orofacial neuropathic pain (2012)
  • Author(s): Kazuo Shibuta, Ikuko Suzuki,
  • Journal Title: Brain Res Volume: 1451 Pages: 74-86
  • DOI: 10.1016/j.brainres.2012.02.023
  • Peer Reviewed
• [Journal Article] Involvement of glial cell activation in modulation of the masticatory movement in freely moving rats with inferior alveolar nerve injury (2012)
  • Author(s): Rahman Md. Mostafeezur, Hossain Md. Zakir,
  • Journal Title: Mol Pain Volume: 8
  • Peer Reviewed
• [Journal Article] Metabotropic glutamate receptor 5 contributes to inflammatory tongue pain via extracellular signal-regulated kinase signaling in the trigeminal subnucleus caudalis and upper cervical spinal cord (2012)
  • Author(s): Ming-Gang Liu, Shingo Matsuura,
  • Journal Title: J Neuroinflammation Volume: 9 Issue: 1 Pages: 258-258
  • DOI: 10.1186/1742-2094-9-258
  • Peer Reviewed
• [Journal Article] Long-term changes in trigeminal ganglionic and thalamic neuronal activities following inferior alveolar nerve transection in awake behaving rats. (2012)
  • Author(s): Wan-Ting Tseng, Meng-Li Tsai,
  • Journal Title: J Neurosci Volume: 32 Issue: 45 Pages: 16051-16063
  • DOI: 10.1523/jneurosci.1828-12.2012
  • Peer Reviewed
• [Journal Article] Differential involvement of two cortical masticatory areas in modulation of the swallowing reflex in rats (2012)
  • Author(s): T Tsujimura, K Tsuji, S Ariyasinghe, T Fukuhara, A Yamada, H Hayashi, Y Nakamura, K Iwata, M Inoue
  • Journal Title: Neurosci Lett Volume: 528(2) Issue: 2 Pages: 159-164
  • DOI: 10.1016/j.neulet.2012.09.005
  • Peer Reviewed
• [Journal Article] Application of capsaicin together with changed sodium channel blocker QX-414 produces transient attenuation of neuropathic-like pain behavior and serves as novel approach for detection of injury related changes in functional expression of TRPV1 channels (2012)
  • Author(s): Hossain Md. Zakir, Rahman Md. Mostafeezur,
  • Journal Title: PLoS One Volume: 7
  • Peer Reviewed
• [Journal Article] P2X3 receptor mediates ectopic mechanical allodynia with inflamed lower lip in mice (2012)
  • Author(s): Masafumi Yasuda, Masamichi Shinoda,
  • Journal Title: Neurosci Lett Volume: 528 Issue: 1 Pages: 67-72
  • DOI: 10.1016/j.neulet.2012.08.067
  • Peer Reviewed
• [Presentation] Mechanisms underlying descending modulation of spinal and medullary nociceptive neurons. (2015)
  • Author(s): Iwata K., Katagiri A., Shinoda M.
  • Organizer: The 120th Annual meeting of the Japanese Association of Anatomists and the 92th Annual metting of the Physiological Society of Japan
  • Place of Presentation: 神戸国際会議場・展示場(兵庫県神戸市）
  • Year and Date: 2015-03-12
  • Invited
• [Presentation] Contribution of Artemin signaling in tongue trigeminal sensory neurons to non-inflammatory tongue pain. (2014)
  • Author(s): Shionda M, Katagiri A, Honda K, Iwata K.
  • Organizer: The 15th world congress on pain
  • Place of Presentation: La Rurd Convention Center(Buenos Aires, Argentina)
  • Year and Date: 2014-11-12
• [Presentation] The role of trigeminal spinal subnucleus caudalis in dry-tongue pain (2014)
  • Author(s): Nakaya Y, Okada A, Tsuboi Y, Shinoda M, Imamura Y, Iwata K
  • Organizer: Society for Neroscience
  • Place of Presentation: Walter E. Washington Convention Center(Washington DC, USA)
  • Year and Date: 2014-11-09
• [Presentation] 初期舌癌の末梢性疼痛抑制に対するエンドセリンの関与 (2014)
  • Author(s): 古川明彦、篠田雅路、本田訓也、玉川崇皓、岩田幸一
  • Organizer: 第56回歯科基礎医学会学術大会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2014-10-01
• [Presentation] 末梢の代謝型グルタミン酸受容体活性化により誘発される熱および機械痛覚過敏に対するTRP channel の関与 (2014)
  • Author(s): 本田訓也、篠田雅路、古川明彦、岩田幸一
  • Organizer: 第56回歯科基礎医学会学術大会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2014-10-01
• [Presentation] 口腔内外における切開処置後の温熱および機械痛覚過敏に対するTRPV1とTRPA1の関与 (2014)
  • Author(s): 浦田健太郎、篠田雅路、岩田幸一
  • Organizer: 第56回歯科基礎医学会学術大会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2014-10-01
• [Presentation] ラット舌癌モデルにおけるエンドセリンの初期癌性疼痛抑制機構 (2014)
  • Author(s): 古川明彦、篠田雅路、本田訓也、岩田幸一
  • Organizer: 第56回歯科基礎医学会学術大会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2014-10-01
• [Presentation] 三叉神経脊髄路核尾側亜核におけるリン酸化ERKの口腔乾燥による舌痛への関与 (2014)
  • Author(s): 中谷有香、坪井美行、篠田雅路、岩田幸一
  • Organizer: 第56回歯科基礎医学会学術大会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2014-10-01
• [Presentation] マウス歯周炎モデルにおける歯周組織の機械痛覚に対するCXCR4 の関与 (2014)
  • Author(s): 長嶋秀和、篠田雅路、難波幸一、高野雅行、芥川秀康、針生恒太郎、好士亮介、菅野直之、岩田幸一
  • Organizer: 第57回秋季日本歯周病学会学術大会
  • Place of Presentation: 神戸国際会議場・展示場(兵庫県神戸市）
  • Year and Date: 2014-09-20
• [Presentation] 口腔乾燥により発生する舌痛に対する三叉神経脊髄路核尾側亜核の役割 (2014)
  • Author(s): 中谷有香、岡田明子、坪井美行、篠田雅路、岩田幸一、今村 佳樹
  • Organizer: 第19回口腔顔面痛学会
  • Place of Presentation: 東京医科歯科大学(東京都文京区）
  • Year and Date: 2014-07-11
• [Presentation] Nitric oxide signaling contributes ectopic orofacial neuropathic pain. (2013)
  • Author(s): Shinoda M, Sugiyama T, Honda K, Kaji K, Urata K, Tamagawa T, Suzuki A, Iwata K.
  • Organizer: Neuroscience 2013
  • Place of Presentation: San Diego（ＵＳＡ）
• [Presentation] Involvement of Artemin and GFRa3 on nociception in rat model of burning mouth syndrome
  • Author(s): Shinoda M. 他
  • Organizer: 8th FENS Forum of neuroscience
  • Place of Presentation: バルセロナ（スペイン）
• [Presentation] Peripheral NMDA receptor contributes cold hyperalgesia via TRPA1
  • Author(s): Honda K. 他
  • Organizer: 8th FENS Forum of neuroscience
  • Place of Presentation: バルセロナ（スペイン）
• [Presentation] ERK phosphorylation of the trigeminal spinal subnucleus neurons contributes facial hyperalgesia with experimental trigeminal mononeuropathy
  • Author(s): Iwata K. 他
  • Organizer: 8th FENS Forum of neuroscience
  • Place of Presentation: バルセロナ（スペイン）
• [Presentation] マウス舌におけるTNBS誘発熱痛覚過敏に対するArteminの役割
  • Author(s): 篠田雅路 他
  • Organizer: 第３４回日本疼痛学会
  • Place of Presentation: 熊本市国際交流会館（熊本）
• [Presentation] ラット眼窩下神経損傷後に発症する二次性痛覚過敏に対するミクログリアの関与
  • Author(s): 澁田一夫 他
  • Organizer: 第３４回日本疼痛学会
  • Place of Presentation: 熊本市国際交流会館（熊本）
• [Presentation] 下歯槽神経切断ラットに発症する異所性機械アロディニアに対する三叉神経節内NOの関与
  • Author(s): 杉山朋久 他
  • Organizer: 第３４回日本疼痛学会
  • Place of Presentation: 熊本市国際交流会館（熊本）
• [Presentation] Satellite glial cell P2Y12 receptor in the trigeminal ganglion is involved in lingual neuropathic pain mechanisms in rats
  • Author(s): Katagiri A. 他
  • Organizer: The 14th world congress on pain
  • Place of Presentation: ミラノ（イタリア）
• [Presentation] Altered artemin signaling in tongue trigeminal sensory neurons contributes to TNBS-induced tongue pain
  • Author(s): Shinoda M. 他
  • Organizer: The 14th world congress on pain
  • Place of Presentation: ミラノ（イタリア）
• [Presentation] Involvement of ERK phosphorylation of the trigeminal spinal subnucleus neurons in facial hyperalgesia in the rats with experimental trigeminal mononeuropathy
  • Author(s): Iwata K. 他
  • Organizer: The 14th world congress on pain
  • Place of Presentation: ミラノ（イタリア）
• [Presentation] Tool-like receptor 4 in the trigeminal sensory neurons is involved in tongue-referred pain following tooth pulp inflammatio
  • Author(s): Ohara K. 他
  • Organizer: The 14th world congress on pain
  • Place of Presentation: ミラノ（イタリア）
• [Presentation] Involvement of ATP, IL-6 and IL-1beta in rat model of masseter muscle pathological pain
  • Author(s): Noma N. 他
  • Organizer: The 14th world congress on pain
  • Place of Presentation: ミラノ（イタリア）
• [Presentation] Fractalkine signaling in microglia contributes orofacial pain induced by trapezius muscle inflammatio
  • Author(s): Kiyomoto M. 他
  • Organizer: The 14th world congress on pain
  • Place of Presentation: ミラノ（イタリア）
• [Presentation] 眼窩下神経結紮ラットの三叉神経脊髄路核尾側亜核細胞におけるERKのリン酸化は温度痛覚過敏に関与する
  • Author(s): 岩田幸一 他
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋国際会議場（愛知）
• [Presentation] プロポフォールによる血管痛に対するTRPA1チャネルの関与
  • Author(s): 宮本真記子 他
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋国際会議場（愛知）
• [Presentation] CFA誘導性歯髄炎により発症する舌の機械痛覚過敏に対するToll-like Receptor4の関与
  • Author(s): 大原絹代 他
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋国際会議場（愛知）
• [Presentation] Peripheral glutamate receptors contribute cold hyperalgesia via TRPA1 mechanisms
  • Author(s): Honda K. 他
  • Organizer: Society for Neuroscience
  • Place of Presentation: New Orleans（米国）
• [Presentation] Contribution of Artemin signaling in tongue trigeminal sensory neurons to TNBS-induced tongue heat hyperalgesia in mice
  • Author(s): Shionda M. 他
  • Organizer: Society for Neuroscience
  • Place of Presentation: New Orleans（米国）
• [Presentation] Involvement of ATP, IL-6 and IL-1beta in rat model of masseter muscle pain
  • Author(s): Noma N. 他
  • Organizer: Society for Neuroscience
  • Place of Presentation: New Orleans（米国）
• [Presentation] 口腔粘膜外傷後の持続痛におけるTRPV2の関与
  • Author(s): 浦田健太郎 他
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: タワーホール船堀（東京）
• [Presentation] 実験的歯牙移動による三叉神経脊髄路核における細胞外シグナル調節キナーゼ（ＥＲK)のリン酸化
  • Author(s): 澁田一夫 他
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: タワーホール船堀（東京）
• [Book] 基礎歯科生理学 (2012)
  • Author(s): 森本俊文、山田好秋編
  • Publisher: 医歯薬出版
• [Book] 歯科生理学実習 (2012)
  • Author(s): 岩田幸一、三枝木泰丈、泰羅雅登、西川泰央編
  • Publisher: 医歯薬出版
• [Remarks] 日本大学歯学部生理学講座
  • URL: http://www.dent.nihon-u.ac.jp/phisio/gs_top.html