A role of purinergic receptor on descending pain modulatory system in anterior cingulate cortex of chronic pain

• Project/Area Number: 23590706
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pain science
• Research Institution: Hirosaki University
• Principal Investigator: MIGITA KEISUKE 弘前大学, 医学(系)研究科(研究院), 助教 (10352262)
• Co-Investigator(Kenkyū-buntansha): UENO Shinya 弘前大学, 大学院医学研究科, 教授 (00312158)
• Co-Investigator(Renkei-kenkyūsha): HONDA Kenji 福岡大学, 薬学部, 助教 (60140761)
• Project Period (FY): 2011-04-28 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 慢性疼痛 / 中枢神経系 / IPSC / プリン受容体 / 中枢 / P2X受容体 / 大脳皮質帯状回 / 下降性抑制系 / GABA

Research Abstract

In this study, we investigated the phenotypes of pain behaviors in phospholipase C-related inactive protein type 1 knockout (PRIP-1-/-) mice that play an important role in trafficking to the plasma membrane of GABAA receptor. PRIP-1-/- mice showed the hyperalgesic responses induced by formalin and von Frey filaments. In situ hybridization studies of GABAA receptors revealed that expression of gamma 2 subunit mRNA was significantly decreased in the dorsal and ventral horn of spinal cord of PRIP-1-/- mice, whereas beta 2 subunit mRNA expression was significantly increased in all areas of the spinal cord. Patch-clamp recordings showed that the function of GABAA receptor in spinal cord was impaired by knockout of PRIP-1. On the other hand, HSP90 regulates the P2X7 current by interacting with the cysteine-rich domain of the cytoplasmic C-terminus. PRIP-1 and P2X7 receptor may become a new drug target for neuropathic pain.

Research Products

• [Journal Article] The kick-in system : a novel rapid knock-in strategy (2014)
  • Author(s): Tomonoh Y, Deshimaru M, Araki K, Miyazaki Y, Arasaki T, Tanaka Y, Kitamura H, Mori F, Wakabayashi K, Yamashita S, Saito R, Itoh M, Uchida T, Yamada J, Migita K, Ueno S, Kitaura H, Kakita A, Lossin C, Takano Y, Hirose S
  • Journal Title: PLoS One Volume: 9
• [Journal Article] Morphologic changes of dendritic spines of striatal neurons in the levodopa-induced dyskinesia model (2014)
  • Author(s): Nishijima H, Suzuki S, Kon T, Funamizu Y, Ueno T, Haga R, Suzuki C, Arai A, Kimura T, Suzuki C, Meguro R, Miki Y, Yamada J, Migita K, Ichinohe N, Ueno S, Baba M, Tomiyama M
  • Journal Title: Mov Disord Volume: 29 Pages: 336-343
• [Journal Article] The kick-in system: a novel rapid knock-in strategy. (2014)
  • Author(s): Tomonoh, Y., Deshimaru, M., Araki, K., Miyazaki, Y., Arasaki, T., Tanaka, Y., Kitamura, H., Mori, F., Wakabayashi, K., Yamashita, S., Saito, R., Itoh, M., Uchida, T., Yamada, J., Migita, K., Ueno, S., Kitaura, H., Kakita, A., Lossin, C., Takano, Y., Hirose, S.
  • Journal Title: PLoS One. Volume: 9 Issue: 2 Pages: 88549-88549
  • DOI: 10.1371/journal.pone.0088549
  • Peer Reviewed / Open Access
• [Journal Article] Morphologic changes of dendritic spines of striatal neurons in the levodopa-induced dyskinesia model (2014)
  • Author(s): Nishijima H, Suzuki S, Kon T, Funamizu Y, Ueno T, Haga R, Suzuki C, Arai A, Kimura T, Suzuki C, Meguro R, Miki Y, Yamada J, Migita K, Ichinohe N, Ueno S, Baba M, Tomiyama M
  • Journal Title: Mov Disord Volume: 29 Suppl 3 Issue: 3 Pages: 336-343
  • DOI: 10.1002/mds.25826
  • Peer Reviewed
• [Journal Article] A novel prophylactic effect of furosemide treatment on autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) (2013)
  • Author(s): Yamada J, Zhu G, Okada M, Hirose S, Yoshida S, Shiba Y, Migita K, Mori F, Sugawara T, Chen L, Liu F, Yoshida S, Ueno S, Kaneko S
  • Journal Title: Epilepsy Res Volume: 107 Pages: 127-137
• [Journal Article] Phospholipase C-related but catalytically inactive protein modulates pain behavior in a neuropathic pain model in mice (2013)
  • Author(s): Kitayama T, Morita K, Sultana R, Kikushige N, Migita K, Ueno S, Hirata M, Kanematsu T
  • Journal Title: Molecular Pain Volume: 9 Pages: 23-23
• [Journal Article] Drebrin immunoreactivity in the striatum of a rat model of levodopa-induced dyskinesia (2013)
  • Author(s): Nishijima H, Arai A, Kimura T, Mori F, Yamada J, Migita K, Wakabayashi K, Baba M, Ueno S, Tomiyama M
  • Journal Title: Neuropathology Volume: 33 Pages: 391-396
• [Journal Article] Properties of a Novel GABA(A) Receptorγ(2) Subunit Mutation Associated With Seizures (2013)
  • Author(s): Migita K, Yamada J, Nikaido Y, Shi X, Kaneko S, Hirose S, Ueno S
  • Journal Title: J Pharmacol Sci Volume: 121(1) Pages: 84-87
• [Journal Article] Phospholipase C-related but catalytically inactive protein modulates pain behavior in a neuropathic pain model in mice (2013)
  • Author(s): Kitayama et al
  • Journal Title: Molecular Pain Volume: 9 Pages: 23-23
  • DOI: 10.1186/1744-8069-9-23
  • Peer Reviewed
• [Journal Article] A novel prophylactic effect of furosemide treatment on autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). (2013)
  • Author(s): Yamada J, Zhu G, Okada M, Hirose S,
  • Journal Title: Epilepsy Res. Volume: 107 Issue: 1-2 Pages: 127-137
  • DOI: 10.1016/j.eplepsyres.2013.08.018
  • Peer Reviewed
• [Journal Article] Drebrin immunoreactivity in the striatum of a rat model of levodopa-induced dyskinesia. (2013)
  • Author(s): Nishijima H, Arai A, Kimura T, Mori F, Yamada J, Migita K, Wakabayashi K, Baba M, Ueno S, Tomiyama M.
  • Journal Title: Neuropathology Volume: 33 Pages: 391-396
  • Peer Reviewed
• [Journal Article] Properties of a Novel GABAA Receptor γ2 Subunit Mutation Associated With Seizures. (2013)
  • Author(s): Migita K, Yamada J, Nikaido Y, Shi X, Kaneko S, Hirose S, Ueno S.
  • Journal Title: Journal of Pharmacological Sciences Volume: 121 Pages: 84-87
  • Peer Reviewed
• [Journal Article] Dysfunction of extrasynaptic GABAergic transmission in phospholipase C-related, but catalytically inactive protein 1 knockout mice is associated with an epilepsy phenotype (2012)
  • Author(s): Zhu G, Yoshida S, Migita K, Yamada J, Mori F, Tomiyama M, Wakabayashi K, Kanematsu T, Hirata M, Kaneko S, Ueno S, Okada M
  • Journal Title: J Pharmacol Exp Ther Volume: 340(3) Pages: 520-528
• [Journal Article] Dysfunction of extrasynaptic GABAergic transmission in phospholipase C-related, but catalytically inactive protein 1 knockout mice is associated with an epilepsy phenotype. (2012)
  • Author(s): Zhu G, Yoshida S, Migita K, Yamada J, Mori F, Tomiyama M, Wakabayashi K, Kanematsu T, Hirata M, Kaneko S, Ueno S, Okada M
  • Journal Title: J Pharmacol Exp Ther Volume: 340 Pages: 520-528
  • Peer Reviewed
• [Journal Article] Phenotypes of pain behavior in phospholipase C-related but catalytically inactive protein type 1 knockout mice (2011)
  • Author(s): Migita K, Tomiyama M, Yamada J, Fukuzawa M, Kanematsu T, Hirata M, Ueno S
  • Journal Title: Mol Pain Volume: 7 Pages: 79-79
• [Journal Article] Phenotypes of pain behavior in phospholipase C-related but catalytically inactive protein type 1 knockout mice. (2011)
  • Author(s): Migita K, Tomiyama M, Yamada J, Fukuzawa M, Kanematsu T, Hirata M, Ueno S.
  • Journal Title: Mol Pain Volume: 7 Pages: 79-86
  • Peer Reviewed
• [Presentation] The intracellular domain of the P2X7 receptor subunit participates in current facilitation and receptor kinetics (2013)
  • Author(s): Keisuke Migita, Junko Yamada, Yoshikazu Nikaido, Shinya Ueno
  • Organizer: Neuroscience2013
  • Place of Presentation: San Diego, USA
  • Year and Date: 2013-11-12
• [Presentation] P2X2受容体のチャネル機能に対する細胞内ドメインの役割 (2013)
  • Author(s): Keisuke Migita, Junko Yamada, Yoshikazu Nikaido, Shinya Ueno
  • Organizer: 第36回日本神経科学大会
  • Place of Presentation: 京都
  • Year and Date: 2013-06-20
• [Presentation] P2X7受容体における細胞内ドメインの機能的特徴 (2013)
  • Author(s): Keisuke Migita, Junko Yamada, Yoshikazu Nikaido, Shinya Ueno
  • Organizer: 第86回薬理学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2013-03-23
• [Presentation] P2X2受容体のチャネル機能に対する細胞内ドメインの役割 (2013)
  • Author(s): 右田啓介
  • Organizer: 第36回日本神経科学大会
• [Presentation] The intracellular domain of the P2X7 receptor subunit participates in current facilitation and receptor kinetics (2013)
  • Author(s): Keisuke Migita
  • Organizer: Neuroscience2013
• [Presentation] The intracellular domain of the P2X7 receptor subunit participates in agonist operation of the channel (2013)
  • Author(s): Keisuke Migita, Junko Yamada, Yoshikazu Nikaido, Shinya Ueno
  • Organizer: 日本薬理学会
  • Place of Presentation: 福岡
• [Presentation] GABA_A receptor via phospholipase C-related but catalytically inactive protein type 1 in the spinal cord participate in abnormal pain sensation (2012)
  • Author(s): Keisuke Migita, Masahiko Tomiyama, Junko Yamada, Yoshikazu Nikaido, Takashi Kanematsu, Masato Hirata, Shinya Ueno Yamada, Yoshikazu Nikaido, Takashi Kanematsu, Masato Hirata, Shinya Ueno
  • Organizer: Neuroscience2012
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2012-10-13
• [Presentation] PRIP-1ノックアウトマウスの痛覚異常は脊髄におけるGABA作動性シナプス伝達異常が関与している (2012)
  • Author(s): Keisuke Migita, Masahiko Tomiyama, Junko
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-09-19
• [Presentation] てんかん患者由来GABA_A受容体g2サブユニット(N40S)変異受容体の薬理学的特性 (2012)
  • Author(s): Keisuke Migita, Junko Yamada, XiuYu Shi, Sunao Kaneko, Shinichi Hirose, Shinya Ueno
  • Organizer: 第85回薬理学会年会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-16
• [Presentation] Hyperalgesia of phospholipase C-related but catalytically inactive protein type 1 knockout mice is induced by the impairment of GABAergic transmission in the spinal cord (2012)
  • Author(s): Keisuke Migita, Masahiko Tomiyama, Junko Yamada, Yoshikazu Nikaido, Takashi Kanematsu, Masato Hirata and Shinya Ueno
  • Organizer: 日本神経科学会
  • Place of Presentation: 名古屋
• [Presentation] GABAA receptor via phospholipase C-related but catalytically inactive protein type 1 in the spinal cord participate in abnormal pain sensation (2012)
  • Author(s): Keisuke Migita, Masahiko Tomiyama, Junko Yamada, Yoshikazu Nikaido, Takashi Kanematsu, Masato Hirata and Shinya Ueno
  • Organizer: Society for Neuroscience
  • Place of Presentation: New Orleans, USA
• [Presentation] てんかん患者由来GABAA受容体γ2サブユニット(N40S)変異受容体の薬理学的特性 (2012)
  • Author(s): 右田啓介
  • Organizer: 日本薬理学会
  • Place of Presentation: 京都国際会館
• [Book] 可塑性と臨床:痛み,Clinical Neuroscience 29(7) (2011)
  • Author(s): 右田啓介, 山田順子, 上野伸哉
  • Publisher: 中外医学社
• [Book] Clinical Neuroscience (2011)
  • Author(s): 右田啓介，山田順子，上野伸哉
  • Total Pages: 3
  • Publisher: 中外医学社
• [Remarks] ホームページ
  • URL: http://www.med.hirosaki-u.ac.jp/~neurophysiol/staff.html
• [Remarks] 弘前大学 大学院医学研究科 脳神経生理学講座
  • URL: http://www.med.hirosaki-u.ac.jp/~neurophysiol/