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

• 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
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• 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 / 疼痛の発生・増強機序 / カイニン酸

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) (2012)
  • Author(s): Miyazaki S, Minami T, Mizuma H, Kanazawa, M, Doi H, Matsumura S, Lu J, Onoe H, Furuta K, Suzuki M and Ito S
  • Journal Title: Eur J Pharmacol Volume: (in press) Issue: 1-3 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
• [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): Miyazaki Shinichiro
  • Organizer: The 14th World Congress on Pain
  • Place of Presentation: Milano Convention Centre （Milan, Italy）
• [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): 宮崎信一郎
  • Organizer: 日本麻酔科学会第59回学術集会
  • Place of Presentation: 神戸国際展示場 （神戸市、兵庫県）
• [Presentation] アクロメリン酸Aによる早期と晩期のアロディニアの比較
  • Author(s): 尾本遥,南敏明,松村伸治,宮﨑信一郎,伊藤誠二
  • Organizer: 日本麻酔科学会第60回学術集会
  • Place of Presentation: 札幌