Internalization and recycling profiles of dimeric opioid receptors induced by remifentanil ; Implication for the mechanism of tolerance and hyperalgesia

• Project/Area Number: 24593059
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Nagasaki University
• Principal Investigator: KURATA Shinji 長崎大学, 病院(歯学系), 助教 (20325666)
• Co-Investigator(Renkei-kenkyūsha): UEZONO Yasuhito 国立研究開発法人国立がん研究センター, 研究所, 分野長 (20213340) ; AYUSE Takao 長崎大学, 医歯薬学総合研究科(歯学系), 教授 (20222705)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 歯科麻酔学

Outline of Final Research Achievements

Remifentanil occasionally induces acute tolerance and postoperative hyperalgesia. Development of acute tolerance and opioid-induced hyperalgesia might be related to accelerated internalization and impaired recycling of μ-opioid receptor (MOR). We thus examined the intracellular localization profiles of MOR induced by remifentanil, and further investigated the effects of co-treatment with S(+)-ketamine and remifentanil on the internalization of MOR with real-time visualizing assay. We demonstrated that higher concentrations of remifentanil caused the acceleration of MOR internalization, which may explain acute tolerance or hyperalgesia after infusion of remifentanil at high concentrations in the clinical settings. Furthermore, we found that co-treatment with S(+)-ketamine prevented the acceleration of MOR internalization induced by remifentanil. Combinational use with S(+)-ketamine and remifentanil may prevent the acute tolerance and postoperative hyperalgesia.

Research Products

• [Journal Article] GABA_B receptors do not internalize after baclofen treatment possibly due to lack of theβ-arrestin association ; a real-time visualization study (2012)
  • Author(s): Sudo, Y., Hojo, M., Ando, Y., Takada, M., Murata, H., Kurata, S., Kanaide, M., Nishida, N., Uezono, Y.
  • Journal Title: Synapse, Epub ahead of print Volume: 66 (9) Issue: 9 Pages: 759-769
  • DOI: 10.1002/syn.21565
  • Peer Reviewed
• [Presentation] remifentanilによるμ-オピオイド受容体の細胞内局在の解析：－Real-time Visualizing Assay― (2014)
  • Author(s): 倉田眞治，達 聖月，讃岐拓郎，鮎瀬卓郎
  • Organizer: 第42回日本歯科麻酔学会総会・学術集会
  • Place of Presentation: 日本歯科大学新潟生命歯学部（新潟市）
  • Year and Date: 2014-10-11 – 2014-10-12