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

瑞芬太尼偶尔会引起急性耐受和术后痛觉过敏。急性耐受和阿片诱导的痛觉过敏的发生可能与μ阿片受体（莫尔）的加速内化和受损的再循环有关。因此，我们研究了瑞芬太尼诱导的莫尔效应的内化和再循环特征。我们进一步研究了S（+）-氯胺酮和瑞芬太尼联合治疗对莫尔内化和再循环的影响。我们证明，较高浓度的瑞芬太尼导致莫尔再循环受损，这可能解释了在临床环境中输注高浓度瑞芬太尼后的急性耐受或痛觉过敏。此外，我们发现，与S（+）-氯胺酮共同治疗可防止瑞芬太尼引起的莫尔循环障碍。S（+）-氯胺酮和瑞芬太尼联合应用可预防急性耐受和术后痛觉过敏。

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 ofμ-opioid receptor(MOR). We thus examined the internalization and recycling profiles of MOR induced by remifentanil. We further investigated the effects of co-treatment with S(+)-ketamine and remifentanil on the internalization and recycling of MOR. We demonstrated that higher concentrations of remifentanil caused impairment of MOR recycling, 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 impairment of MOR recycling induced by remifentanil. Combinational use with S(+)-ketamine and remifentanil may prevent the acute tolerance and postoperative hyperalgesia.