中文摘要：

目的探讨脊髓缝隙连接蛋白43（connexin 43,Cx43）在慢性吗啡镇痛耐受中的作用及其是否通过JNK通路介导慢性吗啡镇痛耐受。方法 Sprague-Dawley（SD）成年♂大鼠连续7 d鞘内注射吗啡10μl（1.5 g.L-1）建立慢性吗啡镇痛耐受模型。采用热辐射甩尾法测定甩尾潜伏期以观察吗啡的镇痛效果。应用Western blot法检测Cx43、磷酸化JNK（p-JNK）、总JNK（t-JNK）、磷酸化c-Jun（p-c-Jun）和总c-Jun（t-c-Jun）的表达;免疫组织荧光染色法检测脊髓Cx43的免疫反应性（immnunoreactivity,IR）。结果吗啡耐受引起大鼠脊髓Cx43的表达明显增多;Gap26（特异性Cx43阻断剂,1.5 g.L-1,10μl）可以拮抗吗啡镇痛耐受,并且明显地抑制慢性吗啡镇痛耐受所致的脊髓JNK及c-Jun的激活。结论脊髓Cx43通过JNK通路介导大鼠慢性吗啡镇痛耐受。

英文摘要：

Aim To investigate the role of spinal connexin 43（Cx43） in the development of chronic morphine antinociceptive tolerance and whether the c-Jun N-terminal kinase（JNK） pathway was involved in this role.Methods Morphine 10 μl（1.5 g · L-1） was adminitered intrathecally for consecutive 7 days to establish the model of chronic analgesic tolerance to morphine in the adult ♂ Sprague-Dawley rats.Hot radiation tail flick test was used to assess the analgesic efficacy.Western blot assay was applied to detect the expressions of Cx43,phosphorylated（p）-JNK,total（t）-JNK,p-c-Jun and t-c-Jun.Results On the 7th day of repeated intrathecal injection of morphine,the expression of Cx43 was remarkably increased in the lumbar spinal cord.Coadministration of Gap26（a specific inhibitor of Cx43,1.5 g · L-1,10 μl） with morphine obviously attenuated not only morphine antinociceptive tolerance,but also the activiation of the JNK and c-Jun induced by chronic morphine treatment.Conclusion The spinal Cx43 mediates morphine antinociceptive tolerance through JNK pathway in rats.