The elucidation of the mechanism of activation in left side and right side of anterior cingulate cortex and the modulation of descending inhibitory pain pathway in chronic pain

• Project/Area Number: 26460693
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pain science
• Research Institution: Fukuoka University (2015-2016); Hirosaki University (2014)
• Principal Investigator: Migita Keisuke 福岡大学, 薬学部, 准教授 (10352262)
• Co-Investigator(Kenkyū-buntansha): 上野 伸哉 弘前大学, 医学研究科, 教授 (00312158)
• Co-Investigator(Renkei-kenkyūsha): HONDA KENJI 福岡大学, 薬学部, 助教 (60140761)
• 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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 慢性疼痛 / 帯状回 / 左右側 / 左右差 / 錐体細胞 / 抑制性神経活動 / 下降性疼痛抑制系 / 中脳水道周囲灰白質

Outline of Final Research Achievements

In this study, we investigated functional changes in anterior cingulate cortex (ACC) of sciatic nerve ligation model mice using biochemical and electrophysiological technique. Spot patterns of the left and the right side of ACC in day 28 after nerve ligation were not same from the result of two-dimensional electrophoresis. These spots included CRMP-2 from the result of mass spectrometry analysis. However, the level of expression of CRMP-2 and pCRMP-2 were not changed between left side and right side of ACC in Western blot analysis. In addition, peak current of mIPSC in fear conditioning rats tended to decrease compared to control rats, whereas the current was not difference between left side and right side in layer II ~ III of pyramidal neuron in ACC. It is possible that excitatory transmission in ACC may be easy to occur by inhibitory system declined in chronic pain and stress condition.

Research Products

• [Journal Article] Activations of muscarinic M1 receptors in the anterior cingulate cortex contribute to the antinociceptive effect via GABAergic transmission. (2017)
  • Author(s): Koga K, Matsuzaki Y, Honda K, Eto F, Furukawa T, Migita K, Irie K, Mishima K, Ueno S.
  • Journal Title: Mol Pain Volume: 印刷中
  • Peer Reviewed
• [Journal Article] HSP90 Regulation of P2X7 Receptor Function Requires an Intact Cytoplasmic C-Terminus. (2016)
  • Author(s): Migita K, Ozaki T, Shimoyama S, Yamada J, Nikaido Y, Furukawa T, Shiba Y, Egan TM, Ueno S.
  • Journal Title: Mol Pharmacol Volume: 90 Pages: 116-126
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] cis-3-Hexenol and trans-2-hexenal mixture prevents development of PTSD-like phenotype in rats. (2016)
  • Author(s): Yoshikazu Nikaido, Junko Yamada, Keisuke Migita, Yuko Shiba, Tomonori Furukawa, Toshihiro Nakashima, Shinya Ueno
  • Journal Title: Behavioural brain research Volume: 297 Pages: 251-258
  • DOI: 10.1016/j.bbr.2015.10.023
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Inhibition of glucose transporter 1 induces apoptosis and sensitizes multiple myeloma cells to conventional chemotherapeutic agents. (2016)
  • Author(s): Matsumoto T, Jimi S, Migita K, Takamatsu Y, Hara S.
  • Journal Title: Leuk Res. Volume: 41 Pages: 103-103
  • DOI: 10.1016/j.leukres.2015.12.008
  • Peer Reviewed
• [Journal Article] Spontaneous epileptic seizures in transgenic rats harboring a human ADNFLE missense mutation in the β2-subunit of the nicotinic acetylcholine receptor. (2015)
  • Author(s): Yuko Shiba, Fumiaki Mori, Junko Yamada, Keisuke Migita, Yoshikazu Nikaido, Koichi Wakabayashi, Sunao Kaneko, Motohiro Okada, Shinichi Hirose, Shinya Ueno
  • Journal Title: Neuroscience research Volume: 100 Pages: 46-54
  • DOI: 10.1016/j.neures.2015.06.003
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Morphological and electrophysiological changes in intratelencephalic-type pyramidal neurons in the motorcortex of a rat model of levodopa-induced dyskinesia. (2014)
  • Author(s): Ueno T, Yamada J, Nishijima H, Arai A, Migita K, Baba M, Ueno s, Tomiyama M.
  • Journal Title: Neurobiology of Disease Volume: 64 Pages: 142-9
  • DOI: 10.1016/j.nbd.2013.12.014
  • Peer Reviewed / Open Access
• [Presentation] 抗がん作用をもつHSP90拮抗薬はP2X7受容体応答を調節する (2017)
  • Author(s): 右田啓介、松本太一、木村公彦、原周司
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-25
• [Presentation] Asymmetrical activity in rat anterior cingulate cortex in fear expression and extinction (2016)
  • Author(s): Tomonori Furukawa, Yoshikazu Nikaido, Keisuke Migita, Shuji Shimoyama, Taku Ozaki, Kohei Koga, and Shinya Ueno
  • Organizer: 第93回日本生理学会大会
  • Place of Presentation: 札幌
  • Year and Date: 2016-03-22
• [Presentation] 衛藤史博、本多健治、東 翔子、浅田 歩、入江圭一、右田啓介、三島健一 (2016)
  • Author(s): ＴＮＦ-αは、糖尿病マウスにおいて機械刺激性痛覚過敏に関与する
  • Organizer: 第８９回薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-09
• [Presentation] Differential effects of propofol and etomidate on hypnotic electroencephalogram stage and sleep-wake cycle in mice (2015)
  • Author(s): Yoshikazu, Nikaido, Sachie, Takada, Tomonori, Furukawa, Keisuke, Migita, Yuko, Shiba, Junko, Yamada, Tetsuya, Kushikata, Kazuyoshi, Hirota, Shuji, Shimoyama, Taku, Ozaki, Kazuhiko, Nakamura, Takashi, Kanematsu, Masato Hirata, Shinya, Ueno
  • Organizer: 第92回日本生理学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] Behavioral Responses to Chronic Restraint Stress in Mice Lacking Phospholipase C-related Inactive Protein Type-1 (2014)
  • Author(s): Nikaido Y., Shimoyama S., Ozaki T., Migita K., Shiba Y., Furukawa T., Yamada J., Kanematsu T., Hirata M., Nakamura K. and Ueno S.
  • Organizer: 第37回日本神経科学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-11 – 2014-09-13