Contribution of stress-induced hypercatecholamine state for the development of postoperative chronic pain

• Project/Area Number: 17K16746
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Anesthesiology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Yamasaki Masaki 京都府立医科大学, 医学(系)研究科(研究院), 助教 (20771520)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 高カテコラミン血症 / ストレス / 痛覚過敏 / 疼痛

Outline of Final Research Achievements

Catecholamine-degrading enzyme COMT inhibitor was administered intraperitoneally. Behavioral analysis showed that hyperalgesia developed in the hypercatecholaminergic model. beta2 adrenergic receptors are expressed in small neurons of the dorsal root ganglia and their expression was increased in the hypercatecholaminergic model. The beta2 adrenergic receptor antagonists had no apparent effect on hyperalgesia caused by hypercatecholaminemia. GRK2, which is involved in the regulation of receptor signaling, tended to increase in the hypercatecholaminergic model, but the change was not statistically significant.

Academic Significance and Societal Importance of the Research Achievements

慢性ストレスは放置すると慢性痛を引き起こしやすく、ストレス誘引性の慢性痛は原因が明らかでなく難治性である。持続的な高カテコラミン血症は慢性ストレス疾患によく観察される症状の一つである。本研究において、高カテコラミン血症が痛覚閾値に影響をあたえ痛覚過敏を誘発することが示された結果、ストレス誘引性慢性痛の治療法に新しい視点を提供することができた。今後、高カテコラミン血症が痛覚過敏を引き起こす分子メカニズムの解明を行う予定である。

Research Products

• [Journal Article] Reduction of the rocuronium-induced withdrawal reflex by MR13A10A, a generic rocuronium with a novel solution: A randomized, controlled study (2019)
  • Author(s): Shimizu Masaru、Amaya Fumimasa、Kinoshita Mao、Yamasaki Masaki、Yokota Isao、Sawa Teiji
  • Journal Title: PLOS ONE Volume: 14 Issue: 10 Pages: 0223947-0223947
  • DOI: 10.1371/journal.pone.0223947
  • Peer Reviewed / Open Access
• [Journal Article] Classification of acute pain trajectory after breast cancer surgery identifies patients at risk for persistent pain: a prospective observational study (2018)
  • Author(s): Okamoto Akiko、Yamasaki Masaki、Yokota Isao、Mori Maiko、Matsuda Megumi、Yamaguchi Yosuke、Yamakita Shunsuke、Ueno Hiroshi、Sawa Teiji、Taguchi Tetsuya、Hosokawa Toyoshi、Amaya Fumimasa
  • Journal Title: Journal of Pain Research Volume: Volume 11 Pages: 2197-2206
  • DOI: 10.2147/jpr.s171680
  • Peer Reviewed / Open Access