The regulation mechanisms of chronic pain via ER-stress pathway in fibromyalgia

• Project/Area Number: 26461476
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Tokyo Medical University
• Principal Investigator: Satoko Aratani 東京医科大学, 医学部, 講師 (40387064)
• Co-Investigator(Kenkyū-buntansha): 中島 利博 東京医科大学, 医学部, 教授 (90260752)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 線維筋痛症 / 疼痛 / 視床下部 / 小胞体ストレス / ミトコンドリア

Outline of Final Research Achievements

Fibromyalgia (FM) is a chronic pain syndrome with unknown etiology. Then the decisive treatments for FM have not been established. We focused on ER stress signals and function of mitochondria in FM. In this study, we attempted to establish the neuron specific synoviolin (SYVN1) deficient mice and an inflammation model mice in the central nerves system (CNS) with HPV vaccine as pathological animal models of FM. Then we analyzed the lesions and pathological mechanisms of FM using these mice and tissues derived from patients with FM. The SYVN1 deficient mice had the morphological abnormality in the CNS. The mouse vaccinated with HPV vaccine showed neurological phenotypes that include low responsiveness of the tail reflex and locomotive mobility. Pathological analyses of these mice revealed the damage to the hypothalamus. These data indicated that these model mice were useful for analyses of FM pathology and the hypothalamus could have important roles for symptoms of FM.

Research Products

• [Journal Article] A Study of Brain Metabolism in Fibromyalgia by Positron Emission Tomography (2017)
  • Author(s): Usui C, Soma T, Hatta K, Aratani S, Fujita H, Nishioka K, Machida Y, Kuroiwa Y, Nakajima T, Nishioka K
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry. Volume: 75 Pages: 120-127
  • DOI: 10.1016/j.pnpbp.2017.01.012
  • Peer Reviewed / Open Access
• [Journal Article] Inhibitory effects of ubiquitination of synoviolin by PADI4 (2017)
  • Author(s): Aratani S, Fujita H, Yagishita N, Yamano Y, Okubo Y, Nishioka K, Nakajima T
  • Journal Title: Mol. Med. Rep Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Murine hypothalamic destruction with vascular cell apoptosis subsequent to combined administration of human papilloma virus vaccine and pertussis toxin (2016)
  • Author(s): Aratani S, Fujita H, Kuroiwa Y, Usui C, Yokota S, Nakamura I, Nishioka K, Nakajima T
  • Journal Title: Sci.Rep Volume: 6 Issue: 1 Pages: 36943-36943
  • DOI: 10.1038/srep36943
  • Peer Reviewed / Open Access
• [Journal Article] A case of fibromyalgia involving pain throughout the body treated with site-specific targeted pain control. (2016)
  • Author(s): Nakajima F, Aratani S, Fujita H, Nakatani K, Makita K, Nakajima T
  • Journal Title: Springerplus Volume: 5 Issue: 1 Pages: 1027-1027
  • DOI: 10.1186/s40064-016-2572-z
  • Peer Reviewed / Open Access
• [Journal Article] Mitochondrial Ubiquitin Ligase Activator of NF-κB (MULAN) regulates NF-κB signaling in ER stress-stimulated cells. (2016)
  • Author(s): Fujita H, Aratani S, Fujii R, Yamano Y, Yagishita N, Araya N, Izumi T, Azakami K, Hasegawa D, Nishioka K and Nakajima T
  • Journal Title: Int J Mol Med. Volume: 37 Issue: 6 Pages: 1611-1618
  • DOI: 10.3892/ijmm.2016.2566
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Synoviolin inhibitor LS-102 reduces endoplasmic reticulum stress-induced collagen secretion in an in vitro model of stress-related interstitial pneumonia. (2015)
  • Author(s): Nakajima F, Aratani S, Fujita H, Yagishita N, Ichinose S, Makita K, Setoguchi Y, Nakajima T.
  • Journal Title: Int J Mol Med. Volume: 35 Issue: 1 Pages: 110-6
  • DOI: 10.3892/ijmm.2014.1984
  • Peer Reviewed / Open Access
• [Journal Article] Effects of xenon irradiation of the stellate ganglion region on fibromyalgia (2015)
  • Author(s): Nakajima F, Komoda A, Aratani S, Fujita H, Kawate M, Nakatani K, Akiyama M, Makita K, Nakajima T.
  • Journal Title: Journal of Physical Therapy Science Volume: 27 Issue: 1 Pages: 209-212
  • DOI: 10.1589/jpts.27.209
  • NAID: 130004835113
  • ISSN: 0915-5287, 2187-5626
  • Peer Reviewed / Open Access
• [Journal Article] The E3 ligase synoviolin controls body weight and mitochondrial biogenesis through negative regulation of PGC-1β. (2015)
  • Author(s): Fujita H, Yagishita N, Aratani S, Saito-Fujita T, Morota S, Yamano Y, Hansson MJ, Inazu M, Kokuba H, Sudo K, Sato E, Kawahara K, Nakajima F, Hasegawa D, Higuchi I, Sato T, Araya N, Usui C, Nishioka K, Nakatani Y, Maruyama I, Usui M, Hara N, Uchino H, Elmer E, Nishioka K, Nakajima T.
  • Journal Title: EMBO J. Volume: 34 Issue: 8 Pages: 1042-55
  • DOI: 10.15252/embj.201489897
  • Peer Reviewed / Open Access
• [Presentation] 関節リウマチにおける転写後修飾による多重化シグナル調節機構の解析 (2016)
  • Author(s): 荒谷聡子、藤田英俊、八木下尚子、山野嘉久、西岡久寿樹、中島利博
  • Organizer: 第3 回 JCR ベーシックリサーチカンファレンス
  • Place of Presentation: アキバプラザ、東京
  • Year and Date: 2016-10-14
• [Presentation] 線維筋痛症における超音波検査の役割 (2016)
  • Author(s): 西森美佐子、山口結花、梅原由加里、中平律子、荒谷聡子、中島若巳、北川中行、中谷孝、中島利博
  • Organizer: 日本線維筋痛症学会 第8回学術集会
  • Place of Presentation: KFC ホール、東京
  • Year and Date: 2016-09-18
• [Presentation] ヒトパピローマウイルスワクチン関連神経免疫異常症候群モデルマウスの解析 (2016)
  • Author(s): 荒谷聡子、藤田英俊、黒岩義之、臼井千恵、西岡久寿樹、中島利博
  • Organizer: 日本線維筋痛症学会 第8回学術集会
  • Place of Presentation: KFC ホール、東京
  • Year and Date: 2016-09-17
• [Presentation] ヒトにおけるシノビオリン阻害剤の効果の検証 (2016)
  • Author(s): 藤田英俊、荒谷聡子、西岡久寿樹、中島利博
  • Organizer: 日本線維筋痛症学会 第8回学術集会
  • Place of Presentation: KFC ホール、東京
  • Year and Date: 2016-09-17
• [Presentation] 線維筋通症における当院の関節超音波検査の取り組みと役割 (2016)
  • Author(s): 西森美佐子、山口結花、梅原由加里、澁谷美雪、荒谷聡子、中島若巳、北川中行、中谷孝、中島利博
  • Organizer: 日本線維筋痛症学会 第8回学術集会
  • Place of Presentation: KFC ホール、東京
  • Year and Date: 2016-09-17
• [Presentation] シノビオリン阻害剤の実用化に向けて (2016)
  • Author(s): 荒谷聡子
  • Organizer: 第17回 運動器科学研究会
  • Place of Presentation: 大阪大学中之島センター、大阪
  • Year and Date: 2016-09-03
• [Presentation] Synoviolin, as a novel factor for understanding obesity and metabolic disorders based on chronic inflammation (2016)
  • Author(s): Aratani S, Nakajima T
  • Organizer: International Conference on Obesity and Chronic Diseases
  • Place of Presentation: Las Vegas, USA
  • Year and Date: 2016-07-26
  • Int'l Joint Research / Invited
• [Presentation] E3 Ubiquitin ligase synoviolin inhibitors has effects on obesity (2016)
  • Author(s): Aratani S, Fujita H, Yagishita N, Yokota M, Nishioka K, Nakajima T
  • Organizer: International Conference on Obesity and Chronic Diseases
  • Place of Presentation: Las Vegas, USA
  • Year and Date: 2016-07-25
  • Int'l Joint Research
• [Presentation] 大腿骨頸部骨折が発症の引き金となった背部痛・咽喉頭部異常感に仙骨硬膜外ブロックが有効であった線維筋痛症の 1 症例 (2015)
  • Author(s): 中島若巳、荒谷聡子、藤田 英俊、中谷孝、中島 利博
  • Organizer: 日本線維筋痛症学会第7回学術集会
  • Place of Presentation: ベルサール新宿
  • Year and Date: 2015-10-03
• [Presentation] 線維筋痛症の心的外傷性ストレスに対する脆弱性: 東日本大震災後 19 ヵ月間の追跡研究 (2015)
  • Author(s): 臼井千恵、西岡健弥、荒谷聡子、藤田英俊、山野嘉久、中島利博、西岡久寿樹
  • Organizer: 日本線維筋痛症学会第7回学術集会
  • Place of Presentation: ベルサール新宿
  • Year and Date: 2015-10-03
• [Presentation] 線維筋痛症における超音波検査の有用性の検討 (2015)
  • Author(s): 西森美佐子、尾崎鈴子、藤島みどり、山口結花、梅原由加里、荒谷聡子、中島若巳、中谷孝、中島利博
  • Organizer: 日本線維筋痛症学会第7回学術集会
  • Place of Presentation: ベルサール新宿
  • Year and Date: 2015-09-12
• [Presentation] 私達が開発した世界初の E3 ユビキチン化酵素シノビオリン阻害剤 LS シリーズの可能性について (2015)
  • Author(s): 荒谷聡子
  • Organizer: 第16回運動器科学研究会
  • Place of Presentation: 南日本新聞社 みなみホール、鹿児島
  • Year and Date: 2015-09-12
• [Presentation] GABA 構造類似薬の副作用による肥満と小胞体ストレスの関与について (2014)
  • Author(s): 荒谷聡子、臼井千恵、藤田英俊、八木下尚子、山野嘉久、西岡健弥、伊藤健司、長田賢一、中村郁朗、西岡久寿樹、中島利博
  • Organizer: 日本線維筋痛症学会 第 6 回学術集会
  • Place of Presentation: ＪＡ長野
  • Year and Date: 2014-09-13 – 2014-09-14
• [Presentation] 小胞体ストレスと線維筋痛症における抗疼痛薬による肥満の関与について (2014)
  • Author(s): 荒谷聡子、山野嘉久、藤田英俊、八木下尚子、伊藤健司、長田賢一、中村郁朗、西岡久寿樹、中島利博
  • Organizer: 第 58 回日本リウマチ学会 総会・学術集会
  • Place of Presentation: グランドプリンスホテル高輪
  • Year and Date: 2014-04-26
• [Book] New Developments in the Pathogenesis of Rheumatoid Arthritis (2017)
  • Author(s): Yagishita N, Aratani S, Fujita H, Yamano Y, Nishioka K, Nakajima T
  • Total Pages: 155
  • Publisher: InTech
• [Remarks] 東京医科大学 医学総合研究所 運動器科学研究部門
  • URL: http://toshinakajima2014.wix.com/tokyomed
• [Remarks] 東京医科大学 医学総合研究所 運動器科学研究部門
  • URL: http://toshinakajima2014.wix.com/tokyomed