The identification of signal pathways inducing the visceral pain of hollow organs and its application to the treatment of visceral hyperesthesia

• Project/Area Number: 26460694
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pain science
• Research Institution: Osaka Prefecture University (2016); Kansai University of Nursing and Health (2014-2015)
• Principal Investigator: Miyai Kazumasa 大阪府立大学, 総合リハビリテーション学研究科, 教授 (60283933)
• Research Collaborator: KAWATANI Masahito ; YOSHIZUMI Masaru ; SHIMADA Shoichi
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 内臓知覚過敏 / アデノシン３リン酸 / 粘膜上皮 / 管腔臓器 / 一酸化窒素 / 環状ヌクレオチド / セロトニン / ATP分泌 / 上皮組織 / cGMP / cAMP / 貯蔵量作動性Ca2+流入 / 5-HT受容体 / PGE2受容体EP1

Outline of Final Research Achievements

The ATP release from mucosal epithelium of hollow organs in response to various stimuli contributes to the visceral sensation. In this study, we examined the effects of 1) PGE2-EP1 pathway, 2) NO-cGMP pathway, and 3) 5-HT receptor pathway on the epithelial ATP release in urinary bladder, esophagus, and colorectum. As a result, we found that NO-cGMP pathway inhibited the epithelial ATP release in all hollow organs analyzed in this study. Then we compared the epithelial ATP release in the model animals of bacterial cystitis or irritable bowel syndrome with that in healthy control animals. In these model animals with visceral hyperesthesia, the epithelial ATP release were increased in comparison to that in control animals.

Research Products

• [Journal Article] Serotonergic regulation of distention-induced ATP release from the urothelium. (2016)
  • Author(s): Matsumoto-Miyai K, Yamada E, Shinzawa E, Koyama Y, Shimada S, Yoshizumi M, Kawatani M.
  • Journal Title: Am. J. Physiol. Renal Physiol. Volume: 310 Issue: 7 Pages: F646-F655
  • DOI: 10.1152/ajprenal.00024.2015
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Authentic role of ATP signaling in micturition reflex. (2016)
  • Author(s): Takezawa K, Kondo M, Kiuchi H, Ueda N, Soda T, Fukuhara S, Takao T, Miyagawa Y, Tsujimura A, Matsumoto-Miyai K, Ishida Y, Negoro H, Ogawa O, Nonomura N, Shimada S.
  • Journal Title: Sci. Rep. Volume: 6 Issue: 1 Pages: 19585-19585
  • DOI: 10.1038/srep19585
  • NAID: 120005818258
  • Peer Reviewed / Open Access
• [Journal Article] Regulatory effects of 5-hydroxytryptamine receptors on voiding function. (2015)
  • Author(s): Matsumoto-Miyai K, Yoshizumi M, Kawatani M.
  • Journal Title: Adv. Ther. Volume: 32 Issue: S1 Pages: 3-15
  • DOI: 10.1007/s12325-015-0240-2
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 膀胱ATPシグナル伝達の生理的・病的意義の検討 (2015)
  • Author(s): 竹澤健太郎，上田倫央，惣田哲次，福原慎一郎，木内寛，宮川康，高尾徹也，辻村晃，根来宏光，松本-宮井和政，近藤誠，島田昌一，野々村祝夫
  • Organizer: 第22回日本排尿機能学会
  • Place of Presentation: 札幌
  • Year and Date: 2015-09-11
• [Presentation] A new mechanism of infection-induced bladder hyperactivity: lipopolysaccharide causes rapid ATP release from urothelium and stimulates the mechanosensory afferent pathway. (2015)
  • Author(s): Takezawa K, Kondo M, Kiuchi H, Soda T, Fukuhara S, Takao T, Miyagawa Y, Tsujimura A, Matsumoto-Miyai K, Shimada S, Nonomura N.
  • Organizer: The 2015 AUA Annual Meeting (AUA2015)
  • Place of Presentation: New Orleans, U.S.A.
  • Year and Date: 2015-05-15
  • Int'l Joint Research
• [Presentation] 細菌性膀胱炎における膀胱知覚亢進の新機構－LPSは炎症とは独立して膀胱上皮のATP放出を惹起しP2X受容体を介してmechanosensitive afferentを活性化する (2015)
  • Author(s): 竹澤健太郎，惣田哲次，福原慎一郎，木内寛，高尾徹也，宮川康，辻村晃，近藤誠，松本-宮井和政，島田昌一，野々村祝夫
  • Organizer: 第103回日本泌尿器科学会総会
  • Place of Presentation: 金沢
  • Year and Date: 2015-04-18