Involvement of medullary GABAergic system in extraterritorial neuropathic pain mechanisms associated with inferior alveolar nerve transection.

• Project/Area Number: 25463151
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Nihon University
• Principal Investigator: OKADA-OGAWA Akiko 日本大学, 歯学部, 准教授 (10434078)
• Co-Investigator(Kenkyū-buntansha): IWATA Kouichi 日本大学, 歯学部, 教授 (60160115) ; SHINODA Masamichi 日本大学, 歯学部, 准教授 (20362238) ; IMAMURA Yoshiki 日本大学, 歯学部, 教授 (90176503)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); 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)
• Keywords: 神経障害性疼痛 / GABA / KCC2 / 三叉神経障害 / 脊髄路核 / 神経科学 / 歯学 / 生理学 / 脳・神経 / シグナル伝達 / 下歯槽神経 / GABA介在神経細胞 / VGAT-Venusラット

Outline of Final Research Achievements

Involvement of the functional changes in the GABAergic system in the trigeminal spinal subnucleus caudalis (Vc) in the mechanisms underlying extraterritorial neuropathic pain in the orofacial region following inferior alveolar nerve transection (IANX) is investigated. It was revealed that GABAergic Vc neurons might be reduced in their number at the early period after IANX and the functional changes might occur in GABAergic neurons from inhibitory to excitatory at the late period after IANX, suggesting that the neuroplastic changes occur in the GABAergic neuronal network in the Vc due to morphological and functional changes at different time periods following IANX and resulting in the extraterritorial neuropathic pain in the orofacial region following trigeminal nerve injury.

Research Products

• [Journal Article] ERK-GluR1 phosphorylation in trigeminal spinal subnucleus caudalis neurons is involved in pain associated with dry tongue (2016)
  • Author(s): Nakaya Y, Tsuboi Y, Okada-Ogawa A, Shinoda M, Kubo A, Chen Jui-Y, Noma N, Batbold D, Imamura Y, Sessle BJ, Iwata K.
  • Journal Title: Mol Pain Volume: in press
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Connexin 43 contributes to ectopic orofacial pain following inferior alveolar nerve injury. (2016)
  • Author(s): Kaji K, Shinoda M, Honda K, Unno S, Shimizu N, Iwata K.
  • Journal Title: Mol Pain. Volume: 8 Pages: 12-12
  • DOI: 10.1177/1744806916633704
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of transient receptor potential vanilloid 1 expression in trigeminal ganglion neurons via methyl-CpG binding protein 2 signaling contributes tongue heat sensitivity and inflammatory hyperalgesia in mice. (2016)
  • Author(s): Suzuki A, Shinoda M, Honda K, Shirakawa T, Iwata K
  • Journal Title: Molecular Pain Volume: 12 Pages: 1-11
  • DOI: 10.1177/1744806916633206
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Recent advances in basic research on the trigeminal ganglion. (2016)
  • Author(s): Goto T, Oh SB, Takeda M, Shinoda M, Sato T, Gunjikake KK, Iwata K.
  • Journal Title: J Physiol Sci. Volume: 29
  • NAID: 40020922519
  • Peer Reviewed
• [Journal Article] Involvement of medullary GABAergic system in extraterritorial neuropathic pain mechanisms associated with inferior alveolar nerve transection. (2015)
  • Author(s): Okada-Ogawa A, Nakaya Y, Imamura Y, Kobayashi M, Shinoda M, Kita K, Sessle BJ, Iwata K.
  • Journal Title: Experimental of Neurology Volume: 28 Pages: 42-52
  • DOI: 10.1016/j.expneurol.2015.02.030
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 舌痛症（バーニングマウス症候群; BMS）の診断と最近の治療方法―舌がヒリヒリ痛む患者さんが来院したら― (2015)
  • Author(s): 岡田明子
  • Journal Title: 東京都歯科医師会雑誌 Volume: 63 Pages: 3-8
• [Journal Article] Involvement of peripheral artemin signaling in tongue pain: possible mechanism in burning mouth syndrome. (2015)
  • Author(s): Shinoda M, Takeda M, Honda K, Maruno M, Katagiri A, Satoh-Kuriwada S, Shoji N, Tsuchiya M, Iwata K.
  • Journal Title: Pain Volume: 156 Pages: 2528-2537
  • Peer Reviewed
• [Journal Article] p38 phosphorylation in medullary microglia mediates ectopic orofacial inflammatory pain in rats. (2015)
  • Author(s): Kiyomoto M, Shinoda M, Honda K, Nakaya Y, Dezawa K, Katagiri A, Kamakura S, Inoue T, Iwata K.
  • Journal Title: Mol Pain. Volume: 12 Pages: 48-48
  • DOI: 10.1186/s12990-015-0053-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Involvement of TRPV1 and TRPA1 in incisional intraoral and extraoral pain. (2015)
  • Author(s): Urata K, Shinoda M, Honda K, Lee J, Maruno M, Ito R, Gionhaku N, Iwata K.
  • Journal Title: J Dent Res. Volume: 94 Issue: 3 Pages: 446-54
  • DOI: 10.1177/0022034514565645
  • 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] TRPA1 contributes to capsaicin-induced facial cold hyperalgesia in rats. (2014)
  • Author(s): Honda K, Shinoda M, Furukawa A, Kita K, Noma N, Iwata K.
  • Journal Title: Eur J Oral Sci. Volume: 122 Issue: 6 Pages: 391-6
  • DOI: 10.1111/eos.12157
  • Peer Reviewed / Open Access
• [Journal Article] Involvement of trigeminal transition zone and laminated subnucleus caudalis in masseter muscle hypersensitivity associated with tooth inflammation. (2014)
  • Author(s): Shimizu K, Matsumoto K, Noma N, Matsuura S, Ohara K, Komiya H, Watase T, Ogiso B, Tsuboi Y, Shinoda M, Hatori K, Nakaya Y, Iwata K.
  • Journal Title: PLoS One. Volume: 9
  • Peer Reviewed / Open Access
• [Journal Article] Involvement of astroglial glutamate-glutamine shuttle in modulation of the jaw-opening reflex following infraorbital nerve injury. (2014)
  • Author(s): Mostafeezur RM, Shinoda M, Unno S, Zakir HM, Takatsuji H, Takahashi K, Yamada Y, Yamamura K, Iwata K, Kitagawa J.
  • Journal Title: Eur J Neurosci. Volume: inpress Issue: 12 Pages: 2050-2059
  • DOI: 10.1111/ejn.12562
  • Peer Reviewed / Open Access
• [Journal Article] Immune and Endocrine Function in Patients with Burning Mouth Syndrome. (2014)
  • Author(s): Koike K., Shinozaki T., Hara K., Noma N., Okada- Ogawa A., Asano M., Shinoda M., Eliav E., Gracely RH., Iwata K. and Imamura Y
  • Journal Title: Clin J Pain Volume: 30 Issue: 2 Pages: 168-173
  • DOI: 10.1097/ajp.0b013e31828c4bf1
  • Peer Reviewed / Open Access
• [Journal Article] predict the success of local anesthetic block after initial treatment by the carbamazepine? (2014)
  • Author(s): Shiiba S, Tanaka T, Sakamoto E, Oda M, Kito S, Ono K, Wakasugi-Sato N, Matsumoto-Takeda S, Seta Y, Imamura Y, Nakanishi O, Inenaga K, Morimoto Y
  • Journal Title: Oral Surg Oral Med Oral Pathol Oral Radiol Volume: 117 Issue: 1 Pages: 15-21
  • DOI: 10.1016/j.oooo.2012.03.029
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy of distortion correction on diffusion imaging: comparison of FSL eddy and eddy_correct using 30 and 60 directions diffusion encoding. (2014)
  • Author(s): Yamada H, Abe O, Shizukuishi T, Kikuta J, Shinozaki T, Dezawa K, Nagano A, Matsuda M, Haradome H, Imamura Y.
  • Journal Title: PLoS One. Volume: 9(11) Issue: 11 Pages: e112411-e112411
  • DOI: 10.1371/journal.pone.0112411
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ラット下歯槽神経切断による神経障害性疼痛に対するGABA介在神経細胞の関与 (2013)
  • Author(s): 岡田明子、鈴木郁子、中谷有香、小林真之、鰻原賀子、今村佳樹、岩田幸一
  • Journal Title: Pain research Volume: 28 Pages: 33-41
  • NAID: 10031165774
  • Peer Reviewed
• [Journal Article] Fractalkine signaling in microglia contributes to ectopic orofacial pain following trapezius muscle inflammation. (2013)
  • Author(s): Kiyomoto M, Shinoda M, Okada-Ogawa A, Noma N, Shibuta K, Tsuboi Y, Sessle BJ, Imamura Y, Iwata K
  • Journal Title: J Neurosci Volume: 33 Issue: 18 Pages: 7667-80
  • DOI: 10.1523/jneurosci.4968-12.2013
  • Peer Reviewed
• [Journal Article] Interaction of IL-1β and P2X3 receptor in pathologic masseter muscle pain. (2013)
  • Author(s): Noma N, Shinoda M, Honda K, Kiyomoto M, Dezawa K, Nakaya Y, Komiyama O, Imamura Y, Iwata K
  • Journal Title: J Dent Res, Volume: 92 Issue: 5 Pages: 456-460
  • DOI: 10.1177/0022034513483770
  • Peer Reviewed
• [Journal Article] Quantitative Evaluation of Eating Oral Function in Peripheral Facial Palsy (2013)
  • Author(s): Kato Y, et al.
  • Journal Title: Clinical Otolaryngology Volume: 未定 Issue: 3 Pages: 231-236
  • DOI: 10.1111/coa.12118
  • Peer Reviewed
• [Journal Article] Involvement of ERK phosphorylation of trigeminal spinalsubnucleus caudalis neurons in thermal hypersensitivity in rats with infraorbital nerve injury. (2011)
  • Author(s): Suzuki I, Honda K (他10名)
  • Journal Title: PLoS One. Volume: 8 Issue: 2 Pages: e57278-e57278
  • DOI: 10.1371/journal.pone.0057278
  • Peer Reviewed
• [Presentation] Studying the neural mechanisms of burning mouth syndrome. (2015)
  • Author(s): Okada-Ogawa A
  • Organizer: 15th scientific meeting of AACMD
  • Place of Presentation: Daegu, Korea
  • Year and Date: 2015-10-25
  • Int'l Joint Research / Invited
• [Presentation] 下垂体腫瘍により口腔顔面痛を引き起こした症例 (2015)
  • Author(s): 岡田明子
  • Organizer: 第19回口腔顔面神経機能学会学術大会
  • Place of Presentation: 日本大学歯学部（東京）
  • Year and Date: 2015-03-07
• [Presentation] 舌痛症に対する治療戦略
  • Author(s): 岡田明子
  • Organizer: 日本レーザー治療学会
  • Place of Presentation: ステーションコンファレンス万世橋（東京）
  • Invited
• [Book] 痛み診療キーポイント―舌痛症 (2014)
  • Author(s): 岡田明子、今村佳樹
  • Total Pages: 264
  • Publisher: 文光堂
• [Book] 痛みの診療ベストプラクティス 5舌咽神経痛 (2014)
  • Author(s): 岡田明子, 今村佳樹
  • Total Pages: 159
  • Publisher: メディカルレビュー社
• [Book] 痛みの診療ベストプラクティス 4舌咽神経痛 (2014)
  • Author(s): 今村佳樹、岡田明子、野間 昇
  • Total Pages: 159
  • Publisher: メディカルレビュー社
• [Book] 口腔顔面痛の診断と治療ガイドブック 3局所麻酔薬 (2013)
  • Author(s): 岡田明子
  • Total Pages: 229
  • Publisher: 医歯薬出版株式会社
• [Book] 新編顎関節症 4疼痛の基本 疼痛の発生メカニズム (2013)
  • Author(s): 岡田明子、今村佳樹
  • Total Pages: 183
  • Publisher: 永末書店