Central neuronal mechanisms for descending antinociception and arousal states in the brain

• Project/Area Number: 26293132
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Pain science
• Research Institution: National Institute for Physiological Sciences
• Principal Investigator: FURUE Hidemasa 生理学研究所, 基盤神経科学研究領域, 准教授(兼任) (20304884)
• Co-Investigator(Kenkyū-buntansha): 神野 尚三 九州大学, 医学(系)研究科(研究院), 教授 (10325524) ; 深澤 有吾 福井大学, 医学部, 教授 (60343745)
• Co-Investigator(Renkei-kenkyūsha): IMOTO Keiji 生理学研究所, 所長 (00176512)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000); Fiscal Year 2016: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2015: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2014: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
• Keywords: 覚醒 / 鎮静 / 鎮痛 / 青斑核 / チャネルロドプシン / 生理学 / 大脳皮質の活動 / 痛覚回路 / GABA / 光遺伝学

Outline of Final Research Achievements

We have studied how noradrenergic neurons in the locus coeruleus in the brain stem act on descending antnociception and arousal levels in the brain. We used virus vectors to control noradrenergic neuronal activity by using optogenetic tools. Locus coeruleus neurons were successfully activated by optic stimulation and how the locus coeruleus activation changes nociceptive behaviors and arousal levels was examined. In vivo electrophysiological analysis was also studied, and the descending and ascending neuronal circuits were identified with Immunohistochemical methods.

Research Products

• [Int'l Joint Research] ブリストル大学(英国)
• [Int'l Joint Research] キョンヒ大学(韓国)
• [Journal Article] Noradrenergic inhibition of spinal hyperexcitation elicited by cutaneous cold stimuli in rats with oxaliplatin-induced allodynia: electrophysiological and behavioral assessments. (2017)
  • Author(s): Choi S, Yamada A, Kim W, Kim SK, Furue H
  • Journal Title: J Physiol Sci Volume: 67(3) Issue: 3 Pages: 431-438
  • DOI: 10.1007/s12576-016-0505-9
  • NAID: 40021176454
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 4-isopropylcyclohexanol has potential analgesic effects through the inhibition of anoctamin 1, TRPV1 and TRPA1 channel activities. (2017)
  • Author(s): Takayama Y, Furue H, Tominaga M.
  • Journal Title: Sci. Rep. Volume: 7 Issue: 1 Pages: 43132-43132
  • DOI: 10.1038/srep43132
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 脳幹における痛みの抑制と慢性疼痛発現の機構 (2017)
  • Author(s): 御領憲治、古江秀昌
  • Journal Title: 医学のあゆみ Volume: 260(2) Pages: 144-148
• [Journal Article] Errata to “Structure-function correlations of rat trigeminal primary neurons: Emphasis on club-like endings, a vibrissal mechanoreceptor” (2016)
  • Author(s): Tonomura S, Ebara S, Bagdasarian K, Uta D, Ahissar E, Meir I, Lampl I, Kuroda D, Furuta T, Furue H, Kumamoto K.
  • Journal Title: Proceedings of the Japan Academy, Series B Volume: 92 Issue: 2 Pages: 76-76
  • DOI: 10.2183/pjab.92.76
  • NAID: 130005125605
  • ISSN: 0386-2208, 1349-2896
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Stimulation of dopamine D2-like receptors in the lumbosacral defecation centre causes propulsive co lorectal contractions in rats. (2016)
  • Author(s): Kiyotada Naitou, Hiroyuki Nakamori, Takahiko Shiina, Azusa Ikeda, Yuuta Nozue, Yuuki Sano, Takuya Yokoyama, Yoshio Yamamoto, Akihiro Yamada, Nozomi Akimoto, Hidemasa Furue, and Yasutake Shimizu
  • Journal Title: The Journal of Physiology Volume: 594 Issue: 15 Pages: 4339-4350
  • DOI: 10.1113/jp272073
  • Peer Reviewed / Open Access
• [Journal Article] Intravenous administration of lidocaine directly acts on spinal dorsal horn and produces analgesic effect: An in vivo patch-clamp analysis. (2016)
  • Author(s): Kurabe M, Furue H, Kohno T
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 26253-26253
  • DOI: 10.1038/srep26253
  • Peer Reviewed / Open Access
• [Journal Article] Changes in synaptic transmission of substantia gelatinosa neurons after spinal cord hemisection revealed by analysis using in vivo patch-clamp recording. (2016)
  • Author(s): Kozuka Y, Kawamata M, Furue H, Ishida T, Tanaka S, Namiki A, Yamakage M
  • Journal Title: Mol Pain Volume: 12 Pages: 1-14
  • DOI: 10.1177/1744806916665827
  • NAID: 120007100116
  • Peer Reviewed / Open Access
• [Journal Article] Involvement of Brain-Enriched Guanylate Kinase-Associated Protein (BEGAIN) in Chronic Pain after Peripheral Nerve Injury. (2016)
  • Author(s): Katano T, Fukuda M, Furue H, Yamazaki M, Abe M, Watanabe M, Nishida K, Yao I, Yamada A, Hata Y, Okumura N, Nakazawa T, Yamamoto T, Sakimura K, Takao T, Ito S.
  • Journal Title: eNeuro Volume: 3(5) Pages: 110-16
  • Peer Reviewed
• [Journal Article] Pain-enhancing mechanism through interaction between TRPV1 and anoctamin 1 in sensory neurons (2015)
  • Author(s): Takayama Y, Uta D, Furue H, Tominaga M
  • Journal Title: Proc Natl Acad Sci USA Volume: 112(16) Pages: 5213-8
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 神経障害性疼痛で生じるCl-イオン濃度勾配はGABAで痛みが生じるほど大きな変化でしょうか？ (2015)
  • Author(s): 山田彬博, 古江秀昌
  • Journal Title: LiSA Volume: 22 Pages: 130-132
• [Journal Article] Three-dimensional distribution of sensory stimulation-evoked neuronal activity of spinal dorsal horn neurons analyzed by in vivo calcium imaging (2014)
  • Author(s): Nishida K, Matsumura S, Taniguchi W, Uta D, Furue H, Ito S.
  • Journal Title: PLoS One Volume: 9(8) Issue: 8 Pages: e103321-e103321
  • DOI: 10.1371/journal.pone.0103321
  • Peer Reviewed / Open Access
• [Presentation] 覚醒下前帯状回皮質感覚応答のIn vivo解析 (2017)
  • Author(s): 山田彬博, 大澤匡弘, 粂和彦, 井本敬二, 古江秀昌
  • Organizer: 94回日本生理学会大会
  • Place of Presentation: アクトシティ浜松（静岡県浜松市）
  • Year and Date: 2017-03-28
• [Presentation] ノルアドレナリン神経による上行性および下行性の痛覚調節機構 (2017)
  • Author(s): 古江秀昌
  • Organizer: 第90回日本薬理学会年会
  • Place of Presentation: 長﨑ブリックホール（長崎県長崎市）
  • Year and Date: 2017-03-15
  • Invited
• [Presentation] Spinal Nociceptive Transmission from the Lower Urinary Tract (2016)
  • Author(s): N.Akimoto, A.Hakozaki, M.Kawatani, K.Imoto, M.Kawatani, H.Furue
  • Organizer: International Association for the Study of Pain (IASP)
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-09-26
  • Int'l Joint Research
• [Presentation] Effects of ethanol on GABAergic synaptic transmission in the rat spinal dorsal horn. (2016)
  • Author(s): A.Yamada, M.Ohsawa, K.Kume, K.Imoto, H.Furue
  • Organizer: International Association for the Study of Pain (IASP)
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-09-26
  • Int'l Joint Research
• [Presentation] Noradrenergic inhibition of spinal hyperexcitation elicited by cutaneous cold stimuli in rats with oxaliplatin-induced allodynia: Electrophysiological and behavioral assessments (2016)
  • Author(s): S. Choi, S. Kim, S. Oh, H. Furue
  • Organizer: International Association for the Study of Pain (IASP)
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-09-26
  • Int'l Joint Research
• [Presentation] Electrophysiological analysis of local anesthetic actions on nociceptive synaptic transmission in the adult rat spinal cord. (2016)
  • Author(s): D.Uta, M.Yoshimura, R.Kawatsu, K.Imoto, H.Furue
  • Organizer: International Association for the Study of Pain (IASP)
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-09-26
  • Int'l Joint Research
• [Presentation] Spinal GABAergic Synaptic Responses Elicited by Optogenetic Activation of Descending Noradrenergic System (2016)
  • Author(s): H.Furue, L.Hickey, Y.Li, A.Pickering, K.Imoto
  • Organizer: International Association for the Study of Pain (IASP)
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-09-26
  • Int'l Joint Research
• [Presentation] 顔面領域刺激による青斑核ノルアドレナリンニューロンの賦活化と痛み伝達の調節 (2016)
  • Author(s): 古江秀昌
  • Organizer: 第93回日本生理学会大会
  • Place of Presentation: 札幌コンベンションセンター，北海道札幌市
  • Year and Date: 2016-03-24
  • Invited
• [Presentation] ANO1阻害剤の検討とそのTRPV1関連疼痛に対する効果 (2016)
  • Author(s): 高山靖規,秋元望,古江秀昌,富永真琴
  • Organizer: 第93回日本生理学会大会
  • Place of Presentation: 札幌コンベンションセンター，北海道札幌市
  • Year and Date: 2016-03-24
• [Presentation] In vivo細胞外記録およびパッチクランプ法を用いた前帯状回皮質感覚応答の解析 (2016)
  • Author(s): 山田彬博, 大澤匡弘, 粂和彦, 井本敬二, 古江秀昌
  • Organizer: 第93回日本生理学会大会
  • Place of Presentation: 札幌コンベンションセンター，北海道札幌市
  • Year and Date: 2016-03-23
• [Presentation] 脳／脊髄ノルアドレナリンネットワーク人為的操作と鎮痛機構の解析 (2016)
  • Author(s): 古江秀昌
  • 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
  • Invited
• [Presentation] Descending pain modulatory system and its activation by systemic alpha 2 agonist (2015)
  • Author(s): Hidemasa Furue
  • Organizer: 12th World congress of Veterinary Anaesthesiology
  • Place of Presentation: 国立京都国際会館，京都府京都市
  • Year and Date: 2015-09-01
  • Int'l Joint Research / Invited
• [Presentation] 下部尿路から脊髄に入力する痛覚伝達機構の in vivo 解析 (2015)
  • Author(s): 秋元望, 箱崎敦志, 河谷正仁, 井本敬二, 古江秀昌
  • Organizer: 第37回日本疼痛学会
  • Place of Presentation: 市民会館崇城大学ホール，熊本県熊本市
  • Year and Date: 2015-07-04
• [Presentation] 髄後角シナプス伝達に対するエタノールの作用 (2015)
  • Author(s): 山田彬博, 大澤匡弘, 粂和彦, 井本敬二, 古江秀昌
  • Organizer: 第37回日本疼痛学会
  • Place of Presentation: 市民会館崇城大学ホール，熊本県熊本市
  • Year and Date: 2015-07-04
• [Presentation] ラット脊髄におけるTRPA1発現線維からの入力を受ける膠様質細胞の発火パターンについて－in vitro及びin vivoパッチクランプ解析を用いて－ (2015)
  • Author(s): 歌大介, 井本敬二, 古江秀昌
  • Organizer: 第37回日本疼痛学会
  • Place of Presentation: 市民会館崇城大学ホール，熊本県熊本市
  • Year and Date: 2015-07-04
• [Presentation] カプサイシン感受性（TRPV1発現）求心性線維によるin vivo感覚シナプス伝達の調節機構 (2015)
  • Author(s): 古江秀昌
  • Organizer: 第92回日本生理学会大会
  • Place of Presentation: 神戸交際会議場・展示場（兵庫県神戸市）
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] Selective excitatory effect of TRPA1 agonists on synaptic transmission in superficial spinal dorsal horn neurons of the adult rat. (2015)
  • Author(s): Uta D, Imoto K and Furue H
  • Organizer: The 88th Annual Meeting of the Japan Pharmacological Society
  • 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] 成熟ラット脊髄後角膠様質ニューロンへの後根刺激誘起のシナプス伝達に対するTRPA1作動薬の応答 (2015)
  • Author(s): 歌 大介, 吉村 恵, 井本敬二, 古江秀昌
  • Organizer: 第36回脊髄機能診断研究会
  • Place of Presentation: JPタワーホール＆カンファレンス（東京都千代田区）
  • Year and Date: 2015-02-07
• [Presentation] Electrophysiological analysis of spinal dorsal horn neurons receiving pruriceptive afferents in the adult rat spinal cord. (2014)
  • Author(s): Uta D, Andoh T, Kuraishi Y, Imoto K and Furue H.
  • Organizer: The 37th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] Action of Chemokine (C-C motif) ligand 1 on synaptic transmission in the spinal superficial dorsal horn. (2014)
  • Author(s): Akimoto N, Uta D, Honda K, Takano Y, Imoto K, Noda M, Furue H
  • Organizer: 2014NIPS-KU/YU Symposium.
  • Place of Presentation: 岡崎カンファレンスセンター（愛知県岡崎市）
  • Year and Date: 2014-07-01 – 2014-07-02
• [Presentation] 下行性疼痛制御機構解明のためのマイルストーン研究 (2014)
  • Author(s): 古江秀昌
  • Organizer: 第36回日本疼痛学会
  • Place of Presentation: KKRホテル大阪（大阪府大阪市）
  • Year and Date: 2014-06-20 – 2014-06-21
  • Invited
• [Presentation] Effects of TRPA1 and TRPV1 agonists on synaptic transmission evoked in morphologically distinct cell types in the substantia gelatinosa of the adult rat spinal cord. (2014)
  • Author(s): Uta D, Imoto K, Furue H
  • Organizer: 第36回日本疼痛学会
  • Place of Presentation: KKRホテル大阪（大阪府大阪市）
  • Year and Date: 2014-06-20 – 2014-06-21
• [Presentation] ラット脊髄後角表層GABAニューロンへの興奮性シナプス入力に対するP2X3受容体の役割 (2014)
  • Author(s): 古賀啓祐, 津田 誠, 井上和秀, 井本敬二, 古江秀昌
  • Organizer: 第36回日本疼痛学会
  • Place of Presentation: KKRホテル大阪（大阪府大阪市）
  • Year and Date: 2014-06-20 – 2014-06-21
• [Presentation] 脊髄後角シナプス伝達に対するCCL-1の作用と疼痛発現機構 (2014)
  • Author(s): 秋元 望, 歌 大介, 本多健治, 高野行夫, 井本敬二, 野田百美, 古江秀昌
  • Organizer: 第36回日本疼痛学会
  • Place of Presentation: KKRホテル大阪（大阪府大阪市）
  • Year and Date: 2014-06-20 – 2014-06-21
• [Presentation] 低用量デクスメデトミジンは逆説的にノルアドレナリン下行性抑制系を賦活化する (2014)
  • Author(s): 舟井優介, 井本敬二, 古江秀昌
  • Organizer: 第36回日本疼痛学会
  • Place of Presentation: KKRホテル大阪（大阪府大阪市）
  • Year and Date: 2014-06-20 – 2014-06-21
• [Presentation] 末梢神経におけるTRV1とアノクタミン１の相互作用による疼痛とその抑制 (2014)
  • Author(s): 高山靖規, 歌 大介, 古江秀昌, 富永真琴
  • Organizer: 第36回日本疼痛学会
  • Place of Presentation: KKRホテル大阪（大阪府大阪市）
  • Year and Date: 2014-06-20 – 2014-06-21
• [Presentation] 電気生理学的及び形態学的解析を用いたラット脊髄膠様質におけるTRPA1及びTRPV1作動薬の作用比較 (2014)
  • Author(s): 歌大介、井本敬二、古江秀昌
  • Organizer: 第36回日本疼痛学会
  • Place of Presentation: KKRホテル大阪（大阪府大阪市）
  • Year and Date: 2014-06-20 – 2014-06-21
• [Presentation] 生理学からみた内因性の鎮痛メカニズム (2014)
  • Author(s): 古江秀昌
  • Organizer: 第６回信州Opioid研究会
  • Place of Presentation: 信州大学医学部旭総合研究棟（長野県松本市）
  • Year and Date: 2014-06-07
  • Invited
• [Remarks] 生理学研究所神経シグナルホームページ
  • URL: http://www.nips.ac.jp/~furue/index.html