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

瑞芬太尼有时会导致急性耐受和术后痛觉过敏。急性耐受和阿片类药物痛敏的发生可能与μ-阿片受体(MOR)内化加速和循环障碍有关。因此，我们研究了瑞芬太尼诱导的MOR的内化和再循环情况。我们进一步研究了S-氯胺酮和瑞芬太尼联合处理对MOR内化和循环的影响。我们证明了较高浓度的瑞芬太尼可导致吗啡循环障碍，这可能是临床输注高浓度瑞芬太尼后出现急性耐受或痛觉过敏的原因。此外，我们还发现，与S-氯胺酮联合处理可阻止瑞芬太尼所致的MOR循环障碍。联合应用S-氯胺酮和瑞芬太尼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.