脊髓星型胶质细胞的JNK介导吗啡耐受

目的观察脊髓JNK在大鼠吗啡镇痛耐受过程中的作用。方法对SD大鼠连续7d鞘内注射吗啡(15μg)建立吗啡耐受的动物模型。采用50℃热水甩尾法观察吗啡的镇痛效果;应用免疫组织化学方法检测吗啡耐受过程中脊髓背角磷酸化JNK(pJNK)的表达情况。结果在慢性鞘内注射吗啡的过程中,大鼠脊髓背角pJNK的表达随着吗啡耐受程度的增加而逐步增加,且pJNK主要存在于脊髓星型胶质细胞。吗啡注射前15min鞘内给予JNK特异性抑制剂SP600125(25μg),不仅可以明显抑制吗啡镇痛耐受还可以部分抑制已形成的吗啡耐受。结论脊髓星型胶质细胞JNK的激活可能是吗啡耐受形成和维持的重要机制之一。

JNK in spinal astrocytes mediates morphine antinociceptive tolerance

Aim To investigate the role of spinal JNK in the development of morphine antinociceptive tolerance.Methods Morphine was administrated intrathecally for consecutive 7 days to achieve analgesic tolerance to morphine.Hot water tail flick tests were used to assess the analgesic efficacy;immunohistochemisty was adopted to detect phosphorylated JNK (pJNK) expression.Results With the development of morphine tolerance,pJNK was gradually upregulated in the lumbar spinal dorsal horn,which mainly existed in astrocytes.Repeated intrathecal injection of a JNK inhibitor (SP600125) 15 min before morphine,not only significantly attenuated the development of morphine antinociceptive tolerance,but also partly inhibited the established tolerance.Conclusion The activation of JNK in spinal astrocytes may be one of the important mechanisms for morphine antinociceptive tolerance.