Analysis of the involvement of Acid-sensing ion channels in post-operative pain enhancement in diabetic patients

• Project/Area Number: 16K10983
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Nagoya City University
• Principal Investigator: Kusama Nobuyoshi 名古屋市立大学, 大学院医学研究科, 講師 (60336691)
• Co-Investigator(Kenkyū-buntansha): 祖父江 和哉 名古屋市立大学, 大学院医学研究科, 教授 (90264738)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: Acid-sensing ion channel / 術後痛 / ASIC / 糖尿病 / イオンチャネル

Outline of Final Research Achievements

In acid-sensing ion channels (ASICs) expressed in CHO cells, the rate of desensitization was altered by changes in extracellular anions. Furthermore, the PH dependence of channel activity was also altered. These changes were different depending on the channel composition. When the amino acid residue at the Cl ion binding site was mutated, the change in channel function by the anion has disappeared. Similar changes were observed in ASICs expressed in rat dorsal root ganglion cells. Anions seems to cause the functional changes depending on the composition of the ASIC channel. Such properties of ASICs suggest that ischemia caused by microangiopathy as a complication of diabetes may modulate the channel activity through changes in extracellular proton and anions.

Academic Significance and Societal Importance of the Research Achievements

酸感受性イオンチャネルには、虚血を感知し痛み信号として脳へ伝えるセンサーの役割がある。この特性は周囲の存在する陰イオンによって影響される。糖尿病の合併症として微小血管障害を生じるが、これによって発生する虚血は、細胞外虚血によるpHと陰イオンの変化を介してチャネル機能を調整している可能性がある。この特徴を利用することで、糖尿病患者における術後痛を軽減する治療法の開発が期待される。

Research Products

• [Presentation] 瞳孔記録計は集中治療室で発症したせん妄を検出できる可能性がある (2019)
  • Author(s): 上村友二、平手博之、伊藤遥、小笠原治、藤掛数馬、仙頭佳起、佐野文昭、井口広靖、草間宣好、祖父江和哉
  • Organizer: 第46回日本集中治療医学会学術集会
• [Presentation] 精神疾患を併存した慢性痛患者の診療における他職種連携の取り組みと経過分析 (2018)
  • Author(s): 太田晴子、浅井明倫、酒井美枝、藤掛数馬、加藤利奈、加古英介、徐民恵、草間宣好、杉浦健之、祖父江和哉
  • Organizer: 日本ペインクリニック学会第52回大会
• [Presentation] Sciatic nerve block as a treatment of lymphedema-induced leg pain (2017)
  • Author(s): Kusama N, Sobue K,
  • Organizer: American Society of Anesthesiologists Annual Meeting 2017
  • Int'l Joint Research