Mechanisms of heat hyper- and hypoalgesia by peripheral metabotropic glutamate receptors

• Project/Area Number: 26460348
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Kanazawa Medical University
• Principal Investigator: NISHIO Matomo 金沢医科大学, 医学部, 教授 (80156041)
• Co-Investigator(Kenkyū-buntansha): 益岡 尚由 金沢医科大学, 医学部, 講師 (80509307)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 代謝型グルタミン酸受容体 / 後根神経節 / 痛覚過敏 / TRPV1 / 後根神経節細胞

Outline of Final Research Achievements

Wounds and inflammation cause glutamate release from primary sensory nerve afferents and damaged cells in the peripheral tissue. In this study, we have revealed that glutamate acts on metabotropic glutamate receptors 1 and 5 (mGluR1/5) in dorsal root ganglion neurons, resulting in potentiation of TRPV1 activities, inhibition of voltage-gated calcium channels and increase of neurons expressing functional TRPV1. These effects are closely associated to multiphasic modulation by glutamate of pain.

Research Products

• [Journal Article] TRPA1 channels modify TRPV1-mediated current responses in dorsal root ganglion neurons (2017)
  • Author(s): Takayoshi Masuoka, Makiko Kudo, Yuka Yamashita, Junko Yoshida, Noriko Imaizumi, Ikunobu Muramatsu, Matomo Nishio, Takaharu Ishibashi.
  • Journal Title: Frontiers in Physiology Volume: 8 Pages: 272-272
  • DOI: 10.3389/fphys.2017.00272
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Pharmacological evidence of specific acetylcholine transport in rat cerebral cortex and other brain regions. (2016)
  • Author(s): Ikunobu Muramatsu, Hatsumi Yoshiki, Junsuke Uwada, Takayoshi Masuoka, Kiyonao Sada, Takanobu Taniguchi, Matomo Nishio.
  • Journal Title: Journal of Neurochemistry Volume: 139 Issue: 4 Pages: 566-575
  • DOI: 10.1111/jnc.13843
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Long-term activation of group I metabotropic glutamate receptors increases functional TRPV1-expressing neurons in mouse dorsal root ganglia (2016)
  • Author(s): Takayoshi Masuoka* , Makiko Kudo, Junko Yoshida, Takaharu Ishibashi, Ikunobu Muramatsu, Nobuo Kato, Noriko Imaizumi and Matomo Nishio
  • Journal Title: Front. Cell. Neurosci. Volume: 10 Pages: 79-79
  • DOI: 10.3389/fncel.2016.00079
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Biphasic modulation by mGlu5 receptors of TRPV1-mediatedintracellular calcium elevation in sensory neurons contributes to heat sensitivity. (2015)
  • Author(s): Masuoka T, Nakamura T, Kudo M, Yoshida J, Takaoka Y, Kato N, Ishibashi T,
  • Journal Title: Br J Pharmacol Volume: 172 Issue: 4 Pages: 1020-1033
  • DOI: 10.1111/bph.12962
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Biphasic modulation of noxious heat sensitivity in sensory neurons by peripheral metabotropic glutamate receptors (2015)
  • Author(s): Masuoka T, Ishibashi T. and Nishio M.
  • Journal Title: Inflamm Cell Signal Volume: 2
  • DOI: 10.14800/ics.602
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Pharmacologically distinct phenotypes of α1B-adrenoceptors: variation in binding and functional affinities for antagonists (2014)
  • Author(s): Yoshiki H, Uwada J, Anisuzzaman ASM, Umada H, Hayashi R, Kainoh M, and Muramatsu I.
  • Journal Title: British Journal of Pharmacology Volume: １７１ Issue: 21 Pages: 4890-4901
  • DOI: 10.1111/bph.12813
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Intracellular localization of the M1 muscarinic acetylcholine receptor through clathrin-dependent constitutive internalization is mediated by a C-terminal tryptophan-based motif. (2014)
  • Author(s): Uwada J, Yoshiki H, Masuoka T, Nishio M, Muramatsu I.
  • Journal Title: J Cell Sci Volume: 127 Pages: 3131-3140
  • Peer Reviewed
• [Presentation] 炎症による代謝型グルタミン酸受容体アゴニスト誘発痛覚行動の増強における神経栄養因子の関与 (2017)
  • Author(s): 益岡尚由、工藤麻希子、吉田純子、山下優香、今泉範子、西尾眞友、石橋隆治
  • Organizer: 第90回日本薬理学会年会
  • Place of Presentation: 長崎ブリックホール（長崎県長崎市）
  • Year and Date: 2017-03-15
• [Presentation] TRPA1 channel modifies membrane current induced by TRPV1 channels activation in dorsal root ganglion neurons. (2016)
  • Author(s): Takayoshi Masuoka, Makiko Kudo, Takaharu Ishibashi, Matomo Nishio
  • Organizer: Society for Neuroscience 2016
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] 神経成長因子による知覚神経のグルタミン酸受容体機能変化 (2016)
  • Author(s): 益岡尚由、吉田純子、工藤麻希子、今泉範子、西尾眞友、石橋隆治
  • Organizer: 第67回日本薬理学会北部会
  • Place of Presentation: 北海道大学学術交流会館(北海道札幌市）
  • Year and Date: 2016-09-30
• [Presentation] Possible contribution of glutamate receptors in ocular hyperalgesia (2016)
  • Author(s): Takayoshi Masuoka, Takaharu Ishibashi, Matomo Nishio
  • Organizer: XXI Biennial Meeting of International Society for Eye Research
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2016-09-25
  • Int'l Joint Research
• [Presentation] 中枢におけるコリン作動性伝達機構 (2016)
  • Author(s): 村松郁延、吉木はつみ、宇和田淳介、益岡尚由、定清直、谷口隆信、西尾眞友
  • Organizer: 第18回応用薬理シンポジウム
  • Place of Presentation: 名古屋大学医学部(愛知県名古屋市)
  • Year and Date: 2016-09-25
• [Presentation] 中枢における新規アセチルコリン伝達機構 (2016)
  • Author(s): 村松郁延、吉木はつみ、宇和田淳介、益岡尚由、定清直、谷口隆信、西尾眞友
  • Organizer: 第20回活性アミンに関するワークショップ
  • Place of Presentation: ホテルマークワンつくば研究学園(茨城県つくば市)
  • Year and Date: 2016-08-20
• [Presentation] Electrophysiological characteristics of TRPV1-mediated responses in TRPA1-positive neurons in dorsal root ganglion (2016)
  • Author(s): Takayoshi Masuoka, Makiko Kudo, Takaharu Ishibashi, Matomo Nishio
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2016-03-10
• [Presentation] Contribution of intracellular acetylcholine receptor to hippocampal long-term potentiation reinforced by an irreversible cholinesterase inhibitor (2016)
  • Author(s): Makiko Kudo, Takayoshi Masuoka, Ikunobu Muramatsu, Matomo Nishio
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2016-03-10
• [Presentation] 短時間および長時間のグルタミン酸受容体活性化による後根神経節細胞のcapsaicinに対する応答性の変化 (2015)
  • Author(s): 益岡尚由、工藤麻希子、吉田純子、石橋隆治、今泉範子、西尾眞友
  • Organizer: 第66回日本薬理学会北部会
  • Place of Presentation: 富山国際会議場（富山県富山市）
  • Year and Date: 2015-09-18
• [Presentation] Effects of the sodium channel blocker amitriptyline on the spontaneous and stimulus-evoked activity of corneal cold-sensitive nerve terminals in intact and tear-deficient guinea-pig eyes. (2015)
  • Author(s): Takayoshi Masuoka, Juana Gallar, Carlos Belmonte
  • Organizer: Association Reseach Vision and Ophthalmology 2015
  • Place of Presentation: Denver, CO, USA
  • Year and Date: 2015-05-02 – 2015-05-07
• [Presentation] Resveratrol Downregulated Caveolin-1 in A431 Cells (2015)
  • Author(s): Noriko Imaizumi, Junko Yoshida, Takaharu Ishibashi, Takayoshi Masuoka, and Matomo Nishio
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] Effects of amitriptyline on the spontaneous and stimulus-evoked activity of corneal cold-sensitive nerve terminals (2015)
  • Author(s): Juana Gallar, Takayoshi Masuoka, Carlos Belmonte
  • Organizer: Association for Ocular Pharmacology and Therapeutics 2015
  • Place of Presentation: Charleston, SC, USA
  • Year and Date: 2015-02-26 – 2015-03-01
• [Book] Muscarinic Receptor: From Structure to Animal Models, Volume 107 of the series Neuromethods (2016)
  • Author(s): Ikunobu Muramatsu, Hatsumi Yoshiki, Kiyonao Sada, Junsuke Uwada, Takanobu Taniguchi, Takayoshi Masuoka, Matomo Nishio
  • Publisher: Springer