Visualization of the change in pain by the autoradiography and calcium imaging in the brain and spinal cord

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659294
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Pain science
• Research Institution: Osaka Medical College
• Principal Investigator: MIYAZAKI SHINICHIRO 大阪医科大学, 医学部, 助教 (30411359)
• Co-Investigator(Kenkyū-buntansha): MORIMOTO Kenji 大阪医科大学, 医学部, 助教 (20388250) ; MINAMI Toshiaki 大阪医科大学, 医学部, 教授 (00257841)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: アロディニア / 神経障害性痛 / アクロメリン酸 / アクロメリン酸誘導体 / オートラジオグラフィー / カルシウムイメージング

Research Abstract

PSPA-4, an acromelic acid (Acro-A) analogue, attenuated the Acro-A-induced allodynia at low doses and induced allodynia at high doses. In vitro autoradiography, [11C]PSPA-4 was specifically bound to the rat brain and spinal cord, and the binding was significantly displaced by kainic acid. And, PSPA-4 increased intracellular Ca2+ concentration of cultured dorsal root ganglion neurons responding to glutamate, much higher than kainate in of them. Taken together, that PSPA-4 attenuated allodynia at low doses and induced allodynia at high doses via a binding site different from known kainate antagonists. In order to visualize the change of pain, a new analogue which has stronger radioactivity is necessary for in vitro autoradiography.
The development of PSPA-4 will enable us to make a break through in the understanding of the action mechanism not only of Acro-A, but also of pain transmission in the periphery and central nervous system.

Research Products

• [Journal Article] The action site of the synthetic kainoid (2S,3R,4R)-3-carboxymethyl-4-(4-methylp henylthio)pyrrolidine-2-carboxylic acid (PSPA-4), an analogue of Japanese mushroom poison acromelic acid, for allodynia (tactile pain) (2013)
  • Author(s): Shinichiro Miyazaki, Toshiaki Minami, Hiroshi Mizuma, Masakatsu Kanazawa, Hisashi Doi, Shinji Matsumura, Jingshan Lu, Hirotaka Onoe, Kyoji Furuta, Masaaki Suzuki, Seiji Ito
  • Journal Title: European Journal of Pharmacology Volume: 710 Pages: 120-127
  • DOI: 10.1016/j.ejphar.2012.10.023
  • Peer Reviewed
• [Presentation] The action site of the synthetic kainoid (2S,3R,4R)-3- carboxymethyl-4-(4-methylphenylthio) pyrrolidine-2-carboxylic acid (PSPA-4), an analogue of Japanese mushroom poison acromelic acid, for allodynia (tactile pain) (2012)
  • Author(s): Shinichiro Miyazaki
  • Organizer: 14Th World Congress on Pain
  • Place of Presentation: ミラノ市
  • Year and Date: 2012-08-29
• [Presentation] アクロメリン酸誘導体を用いたオートラジオグラフィー・カルシウムイメージングによる脳・脊髄の痛みの可視化～新たな神経因性疼痛治療薬へのアプローチ～ (2012)
  • Author(s): 宮﨑信一郎
  • Organizer: 日本麻酔科学会第59回学術集会
  • Place of Presentation: 神戸市
  • Year and Date: 2012-06-07