Identification of the role of spino-parabrachio-amygdaloid pathway in the pain-associated emotion

2016 Fiscal Year Annual Research Report

• Project/Area Number: 25293136
• Research Institution: Jikei University School of Medicine
• Principal Investigator: 加藤 総夫 東京慈恵会医科大学, 医学部, 教授 (20169519)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: 扁桃体 / 腕傍核 / 恐怖学習 / 慢性痛 / 情動 / アロディニア / 光遺伝学 / 化学遺伝学

Outline of Annual Research Achievements

今年度は昨年度末に投稿し、査読者とのやり取りを経て受理されるに至った論文をopen access化した。研究成果は平成27年度末までに得られており、平成27年度の研究実績の概要に示した。要約すると（１）マウス腕傍核ー扁桃体路の光遺伝学的活性化は恐怖学習を成立させる、（２）腕傍核内チャネルロドプシン２発現ラットの扁桃体スライスにおける腕傍核ー扁桃体投射ニューロン終末の光刺激は、扁桃体中心核ニューロンに単シナプス性、および、他シナプス性のネットワーク活動を介した活動を生じさせる、ならびに、（３）ラット炎症性疼痛は扁桃体中心核シナプス伝達増強と全身性痛覚過敏を生じる、が明らかにされた。
その後に進めた化学遺伝学法ならびに新規に作製したVGAT-Creラットを用いた研究によって、右扁桃体中心核のニューロン興奮性が全身性の疼痛閾値の制御に関与している事実を示した。これは、本研究課題によって証明された、痛みが恐怖情動の責任核である扁桃体を活性化させるのみならず、その結果として、おそらくは下行性疼痛制御系の活動を変容させることによって、侵害受容に対する感受性を末梢～脊髄レベルで変化させる可能性が示された。この研究成果は、外部からの侵害刺激に対する感受性や閾値を、炎症や傷害などの身体の状態に呼応して扁桃体が制御している可能性を意味しており、「情動」の生物学意義・起源を考える上で極めて興味深く、「痛み」を超えた広汎的生存戦略としての重要性を示唆している。今後のさらなる研究の推進が必要である。

Research Progress Status

28年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

28年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] NeuroSpin, CEA(France)
  • Country Name: France
  • Counterpart Institution: NeuroSpin, CEA
• [Int'l Joint Research] 4th Military Medical School(China)
  • Country Name: China
  • Counterpart Institution: 4th Military Medical School
• [Int'l Joint Research] The Institute of Science and Technology(オーストリア)
  • Country Name: AUSTRIA
  • Counterpart Institution: The Institute of Science and Technology
• [Int'l Joint Research] NIH/NCCIH(米国)
  • Country Name: U.S.A.
  • Counterpart Institution: NIH/NCCIH
• [Journal Article] Facilitation of distinct inhibitory synaptic inputs by chemical anoxia in neurons in the oculomotor, facial and hypoglossal motor nuclei of the rat (2017)
  • Author(s): Takagi S, Kono Y, Nagase M, Mochio S, Kato F
  • Journal Title: Exp Neurol Volume: 290 Pages: 95-105
  • DOI: 10.1016/j.expneurol.2017.01.007
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Overlapping memory trace indispensable for linking, but not recalling, individual memories. (2017)
  • Author(s): Yokose J, Okubo-Suzuki R, Nomoto M, Ohkawa N, Nishizono H, Suzuki A, Matsuo M, Tsujimura S, Takahashi Y, Nagase M, Watabe AM, Sasahara M, Kato F, Inokuchi K
  • Journal Title: Science Volume: 355 Pages: 398-403
  • DOI: 10.1126/science.aal2690
  • Peer Reviewed / Open Access
• [Journal Article] Potentiation of NMDA receptor-mediated synaptic transmission at the parabrachial-central amygdala synapses by CGRP in mice (2017)
  • Author(s): Okutsu Y, Takahashi Y, Nagase M, Shinohara K, Ikeda R, Kato F
  • Journal Title: Molecular Pain Volume: 印刷中 Pages: 印刷中
  • DOI: in press
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Synaptic and network consequences of monosynaptic nociceptive inputs of parabrachial nucleus origin in the central amygdala (2016)
  • Author(s): Sugimura YK, Takahashi Y, Watabe AM, Kato F
  • Journal Title: J Neurophysiol Volume: 115 Pages: 2721-39
  • DOI: 10.1152/jn.00946.2015
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cellular tagging as a neural network mechanism for behavioral tagging (2016)
  • Author(s): Nomoto M, Ohkawa N, Nishizono H, Yokose J, Suzuki A, Matsuo M, Tsujimura S, Takahashi Y, Nagase M, Watabe AM, Kato F, Inokuchi K
  • Journal Title: Nat Commun Volume: 7 Pages: 12319
  • DOI: 10.1038/ncomms12319
  • Peer Reviewed / Open Access
• [Journal Article] Distinct effects of isoflurane on basal BOLD signals in tissue/vascular microstructures in rats (2016)
  • Author(s): Tsurugizawa T, Takahashi Y, Kato F
  • Journal Title: Scientific Reports Volume: 6 Pages: 38977
  • DOI: 10.1038/srep38977
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 侵害受容と痛み情動-痛みの慢性化における扁桃体の役割 (2017)
  • Author(s): 高橋由香里, 杉本真理子, 宮沢祐太, 杉村弥恵, 篠原恵, 渡部文子, 加藤総夫.
  • Organizer: 第94回日本生理学会大会
  • Place of Presentation: 浜松
  • Year and Date: 2017-03-29 – 2017-03-29
• [Presentation] ラット炎症性疼痛モデル異所性アロディニアへの扁桃体中心核の関与 (2017)
  • Author(s): 杉本真理子, 杉村弥恵, 宮沢祐太, 高橋由香里, 渡部文子, 加藤総夫
  • Organizer: 第94回日本生理学会大会
  • Place of Presentation: 浜松
  • Year and Date: 2017-03-28 – 2017-03-28
• [Presentation] 慢性痛関連症候を視る・測る・操作する (2017)
  • Author(s): 加藤総夫
  • Organizer: 第90回日本薬理学会年会
  • Place of Presentation: 長崎
  • Year and Date: 2017-03-17 – 2017-03-17
• [Presentation] 下肢アロデニア成立における扁桃体中心核の役割 (2017)
  • Author(s): 杉本真理子, 高橋由香里, 加藤総夫.
  • Organizer: 生理研研究会 『痛みの理解を目指した先端的アプローチ』
  • Place of Presentation: 岡崎
  • Year and Date: 2017-01-30 – 2017-01-30
• [Presentation] Optogenetic dissection of the amygdala-mediated control of the descending pain modulation (2016)
  • Author(s): Sugimura YK, Ghasemi Z, Takahashi Y, Yanagawa Y, Kaneko R, Watabe AM, Kato F
  • Organizer: Society for Neuroscience Annual Meeting 2016
  • Place of Presentation: San Diego
  • Year and Date: 2016-11-15 – 2016-11-15
  • Int'l Joint Research
• [Presentation] 炎症性疼痛モデル持続性異所性痛覚過敏成立における扁桃体中心核の役割 (2016)
  • Author(s): 杉本真理子, 杉村弥恵, 宮沢祐太, 高橋由香里, 渡部文子, 加藤総夫
  • Organizer: 第9回日本運動器疼痛学会
  • Place of Presentation: 東京
  • Year and Date: 2016-11-15 – 2016-11-15
• [Presentation] 痛みの慢性化に伴う脳内情動疼痛回路のアロスタシス的障害 (2016)
  • Author(s): 加藤総夫
  • Organizer: 第31回日本整形外科学会基礎学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2016-10-13 – 2016-10-16
  • Invited
• [Presentation] Non-amino acid neuromodulators regulate inflammation-induced generalized sessitization and voluntary choice of preferred environment (2016)
  • Author(s): Sugimoto, Y., Takahashi, Y., Miyazawa, Y., Watabe, A., Kato, F.
  • Organizer: The 16th World Congress on Pain
  • Place of Presentation: 横浜
  • Year and Date: 2016-09-30 – 2016-09-30
  • Int'l Joint Research
• [Presentation] Fearing the pain: the parabrachio-amygdaloid pathway in aversive memory and pain chronification (2016)
  • Author(s): Kato F
  • Organizer: The 16th World Congress on Pain
  • Place of Presentation: 横浜
  • Year and Date: 2016-09-30 – 2016-09-30
  • Int'l Joint Research
• [Presentation] Pathway-dependent differential effects of pregabalin on the excitatory inputs to the nociceptive amygdala in mice with inflammatory pain (2016)
  • Author(s): Yamamoto S, Takahashi Y, Watabe AM, Kato F
  • Organizer: The 16th World Congress on Pain
  • Place of Presentation: 横浜
  • Year and Date: 2016-09-30 – 2016-09-30
  • Int'l Joint Research
• [Presentation] Plasticity in the parabrachial-amygdala circuit and its consequence in pain chronification (2016)
  • Author(s): Kato F
  • Organizer: Brain and New Pain Mechanisms, Satellite Symposium of 16th World Congress of Pain
  • Place of Presentation: 東京
  • Year and Date: 2016-09-25 – 2016-09-25
  • Int'l Joint Research / Invited
• [Presentation] 慢性腰痛と扁桃体可塑性 (2016)
  • Author(s): 加藤総夫
  • Organizer: 第24回日本腰痛学会
  • Place of Presentation: 甲府
  • Year and Date: 2016-09-03 – 2016-09-03
  • Invited
• [Presentation] ホルマリン炎症遷延性疼痛モデルを用いた脳内慢性化過程の解析 (2016)
  • Author(s): 加藤総夫
  • Organizer: 第36回鎮痛薬オピオイドペプチドシンポジウム
  • Place of Presentation: 札幌
  • Year and Date: 2016-08-20 – 2016-08-20
  • Invited
• [Presentation] 炎症性疼痛モデルラットにおける扁桃体-中脳水道周囲灰白質シナプス伝達 (2016)
  • Author(s): 高橋由香里, Ghaseme Z, 杉村弥恵, 篠原 恵, 加藤総夫
  • Organizer: 第36回鎮痛薬オピオイドペプチドシンポジウム
  • Place of Presentation: 札幌
  • Year and Date: 2016-08-20 – 2016-08-20
• [Presentation] Dendritic integration of excitatory inputs of distinct origins to distinct dendrite compartments in the central amygdala (2016)
  • Author(s): Nagase, M., Watabe, A. M., Kato, F.
  • Organizer: The 39th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: 横浜
  • Year and Date: 2016-07-22 – 2016-07-22
• [Presentation] Visualization of spontaneous brain activity during pain chronification process with manganeseenhanced magnetic resonance imaging (MEMRI) (2016)
  • Author(s): Shinohara, Kei., Takahashi, Y., Tsurugizawa, T., Ikeda, R., Marumo, K., Kato, F.
  • Organizer: The 39th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: 横浜
  • Year and Date: 2016-07-22 – 2016-07-22
• [Presentation] Neural circuits underlying flight-or-freeze behavior triggered by an environmental threat. (2016)
  • Author(s): Ito M, Nagase M, Sugimura YK, Takahashi Y, Watabe AM, Kato F
  • Organizer: The 39th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: 横浜
  • Year and Date: 2016-07-21 – 2016-07-21
• [Presentation] Role of the amygdala in early phase of the central pain chronification (2016)
  • Author(s): Takahashi, Y., Miyazawa, Y., Sugimura, Y. K., Sugimoto, M. Shinohara, K., Ghasemi, Z., Watabe, A.M., Kato, F.
  • Organizer: The 39th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: 横浜
  • Year and Date: 2016-07-21 – 2016-07-21
• [Presentation] Amygdala CGRP receptors affect ectopic mechanical hypersensitivity of hindpaws in the orofacial inflammatory pain model (2016)
  • Author(s): Sugimoto M, Miyazawa Y, Takahashi Y, Kato F
  • Organizer: The 10th FENS Forum of Neuroscience
  • Place of Presentation: Copenhagen
  • Year and Date: 2016-07-03 – 2016-07-03
  • Int'l Joint Research
• [Presentation] Early chronification process in inflammatory pain; involvement of amygdala plasticity (2016)
  • Author(s): Kato F
  • Organizer: Pain Mechanisms and Therapeutics Conference
  • Place of Presentation: Sicily, Italie
  • Year and Date: 2016-06-05 – 2016-06-10
  • Int'l Joint Research
• [Presentation] 疼痛と情動の脳内機構 (2016)
  • Author(s): 加藤総夫
  • Organizer: 第23回脳機能とリハビリテーション研究会学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2016-04-24 – 2016-04-24
  • Invited
• [Remarks] 痛み情報がどのように情動回路を活性化するか解明！
  • URL: http://www.jikei-neuroscience.com/website/2017/05/post-fb43.html
• [Remarks] 身体に及ぶ危険・脅威を学習させる信号経路を解明！
  • URL: http://www.jikei-neuroscience.com/website/2017/05/post-9537.html