| Budget Amount *help |
¥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)
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| 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.
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