脊髓c-Jun在NMDA受体NR2B亚基介导的大鼠吗啡镇痛耐受中的作用

Role of c-Jun of spinal cord in NMDA receptor subunit NR2B mediated morphine antinociceptive tolerance in rats

目的探讨脊髓c-Jun在N-甲基-D-天冬氨酸(N-meth-yl-D-aspartate,NMDA)受体NR2B亚基介导的吗啡镇痛耐受中的作用。方法取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。应用热水甩尾法测定甩尾潜伏期(疼痛指标)以观察痛反应变化。应用免疫组织化学染色法检测磷酸化c-Jun(p-c-Jun)和总c-Jun(t-c-Jun)的表达。结果鞘内注射吗啡7 d,可激活大鼠脊髓的c-Jun,表现为神经元内p-c-Jun表达升高;鞘内注射NR2B选择性拮抗剂10μl Ro256981(2 g.L-1)可以抑制慢性吗啡镇痛耐受时脊髓神经元c-Jun的激活,并明显拮抗吗啡镇痛耐受的形成。结论脊髓神经元c-Jun的磷酸化参与NMDA受体NR2B亚基介导的吗啡镇痛耐受。

Aim To investigate the role of spinal cord c-Jun in the development of N-methyl-D-aspartate（NMDA）receptor subunit NR2B mediated morphine antinociceptive tolerance.Methods Morphine 10 μl（1.5 g·L-1） was administered intrathecally for consecutive 7 days to achieve analgesic tolerance to morphine.Hot water tail flick test was used to assess the analgesic efficacy.Immunohistochemistry assay was applied to detect the expressions of phosphorylated c-Jun（p-c-Jun） and total c-Jun（t-c-Jun）.Results At the 7th day of repeated intrathecal injection of morphine,c-Jun was activated remarkably in the lumbar spinal cord,which mainly existed in neurons.Repeated intrathecal injection of the NR2B competitive inhibitor Ro256981 10 μl（2 g·L-1）coadministrated with morphine not only partly inhibited the activation of c-Jun induced by chronic morphine treatment,but also markedly attenuated the development of morphine antinociceptive tolerance.Conclusion The spinal cord neuron p-c-Jun contributes to NMDA receptor subunit NR2B mediated morphine antinociceptive tolerance.