脊髓Cx43通过JNK通路介导大鼠慢性吗啡镇痛耐受

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。

Spinal Cx43 mediates chronic morphine antinociceptive tolerance through JNK pathway in rats

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.