Involvement of the kappa-opioid receptor in nitrous oxide-induced analgesia in mice.
Involvement of the kappa-opioid receptor in nitrous oxide-induced analgesia in mice.
复制标题
kappa-阿片受体参与一氧化二氮诱导的小鼠镇痛。
作者：
小山智弘;福田和彦
一氧化二氮（N2 O）诱导的镇痛作用被认为是由内源性阿片类物质介导的。我们先前使用基因敲除方法表明，N2 O在小鼠中的镇痛作用不需要μ-阿片受体。在这项研究中，我们研究了κ-（KOP）-或δ-阿片受体（DOP）-选择性拮抗剂对N2 O诱导的镇痛作用的影响。采用扭体法评价N_2O的镇痛作用。将7-8周龄的雄性C57 BL/6小鼠分配到对照组、N2 O组、KOP激动剂组和DOP激动剂组。根据分组，用KOP拮抗剂去甲-binaltorphimine（nor-BNI）、DOP拮抗剂盐酸纳曲吲哚（NTI）、KOP激动剂U 50488和DOP激动剂SNC 80预处理小鼠。对照组、KOP激动剂组和DOP激动剂组小鼠暴露于25%氧气/75%氮气中30 min，N2 O组小鼠暴露于25%氧气/75% N2 O中30 min。Nor-BNI [10 mg kg-1，皮下（s.c.）]显著抑制N2 O和U 50488的镇痛作用。NTI（10 mg kg-1s.c.）对N_2O的镇痛作用无明显影响，但几乎完全抑制SNC_（80）的镇痛作用。这些结果提示KOP在N_2O的镇痛作用中起重要作用。
Nitrous oxide (N2O)-induced analgesia is thought to be mediated by endogenous opioids. We previously showed that the μ-opioid receptor is not required for the analgesic action of N2O in mice using a gene knockout approach. In this study, we examined the effect of κ- (KOP)- or δ-opioid receptor (DOP)-selective antagonists on N2O-induced analgesia. The analgesic effect of N2O was evaluated using a writhing test. Male C57BL/6 mice aged 7–8 weeks were assigned to control, N2O, KOP agonist, and DOP agonist groups. According to the group assignment, mice were pretreated with a KOP antagonist, nor-binaltorphimine (nor-BNI), a DOP antagonist, naltrindole hydrochloride (NTI), a KOP agonist U50488, and a DOP agonist SNC80. Mice in the control, KOP agonist, and DOP agonist groups were exposed to 25% oxygen/75% nitrogen for 30 min, and mice in the N2O group were exposed to 25% oxygen/75% N2O for 30 min. Nor-BNI [10 mg kg–1, subcutaneously (s.c.)] significantly suppressed the analgesic effect of N2O and U50488. In contrast, NTI (10 mg kg–1s.c.) did not significantly affect the analgesic action of N2O, but almost completely inhibited the analgesic effect of SNC80. These results suggest that KOP plays an important role in the analgesic effect of N2O in mice.