脊神经结扎模型大鼠双足痛阈变化与脊髓促炎因子表达的相关性

Relationship between bilateral paw mechanical pain and the proinflammatory expression in spinal cord in a rat model of spinal nerve ligation

目的:分析脊神经结扎模型(SNL)大鼠脊髓IL-1β、IL-6 mRNA的表达与双足痛觉敏化和异常疼痛发生发展的关系。方法:选择健康成年清洁级雄性SD大鼠24只,随机分为脊神经结扎组、假手术组、对照组,用up-down方法测定50%机械缩足反应阈值(mechanical paw withdrawal threshold,MWT),观察痛阈变化趋势;RT-qPCR分别检测不同时点L5-L6左、右侧脊髓背角IL-1β、IL-6 mRNA的表达水平。结果:L5、L6脊神经结扎后3天,手术侧足50%MWT明显降低(P<0.001),至术后21天达最低峰值(P<0.001);与手术侧足相比,对侧足痛敏增加仅在术后10天、14天有统计学意义(P<0.01,P<0.05)。与假手术组、对照组相比,脊神经结扎后7天,手术侧脊髓背角IL-1βmRNA的表达明显增加(P<0.05);脊神经结扎后7天、14天,手术侧脊髓背角IL-6 mRNA的表达增加(P<0.05),术后7天的表达水平高于术后14天,但无统计学差异;脊神经结扎后10天、14天,与假手术组相比,非手术侧脊髓背角IL-1β、IL-6 mRNA的含量有增高趋势,但差异无统计学意义。结论:L5、L6结扎后,双足均发生痛觉敏化和异常性疼痛现象,但结扎侧足出现痛敏的时间早且持续时间长;脊髓中IL-1β、IL-6 mRNA随着时间的进程而具有不同的表达特点,对神经病理性疼痛的产生和发展发挥着一定的作用。

Objective： To analyze the mRNAs expression of IL-1β,IL-6 in spinal dorsal horn and their effects on mechanical pain sensitivity following spinal nerve ligation in rats.Methods： Healthy adult male SD rats were randomly divided into the spinal nerve ligation group（Tx）,sham operation group（S）,control group.The 50% mechanical paw withdrawal threshold（50%MWT） of left or right feet was determined by up-down method;RT-qPCR measured the mRNA expression levels of IL-1β and IL-6 in left or right spinal dorsal horn at different time point after surgery.Results： The 50%MWT of ipsilateral feet decreased significantly on 3rd day after L5 and L6 spinal nerve ligation（P0.001） and reached the minimum on 21st day（P0.001）.The mechanical pain sensitivity of the contralateral feet enhanced significantly only on 10th day and 14th day after nerve ligation（P0.01,P0.05）.The mRNA expression of IL-1β and IL-6 upregulated in ipsilateral dorsal horn on 7th day after nerve ligation when compared to group S or control group（P0.05）;on 14th day,the level of IL-6 mRNA in ipsilateral side was still higher than group S or control group（P0.05）.The mRNAs of IL-1β,IL-6 in contralateral spinal dorsal horn showed no significant increase on 10th,14th day after nerve ligation.Conclusion： Unilateral L5 and L6 nerve ligation contributed to mechanical hyperalgesia development of bilateral feet,however,the mechanical pain sensitivity of ipsilateral feet after nerve ligation occurred earlier and maintained longer.IL-1β、IL-6 mRNA in bilateral spinal dorsal horn showed different characteristic expression in the time course,they played an important role in neuropathic pain.