METHODS: Intrathecal (IT) catheter implantation and SNL were used for drug administration and pain model in male Sprague-Dawley rats. The effect of gastrodin or MCC950 (NLRP3 inflammasome inhibitor) on mechanical allodynia was measured by von Frey test. Changes in NLRP3 inflammasome components and interleukin-1β (IL-1β) and cellular expression were examined in the spinal cord and dorsal root ganglion.
RESULTS: The expression of NLRP3 inflammasome components was found mostly in the neurons in the spinal cord and dorsal root ganglion. The protein and mRNA levels of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and IL-1β were upregulated in SNL animals compared to Sham animals. IT administration of GAS significantly attenuated the expression of NLRP3 inflammasome and the intensity of SNL-induced mechanical allodynia. NLRP3 inflammasome inhibitor, MCC950, also attenuated the intensity of allodynia, but the effect is less strong and shorter than that of GAS.
CONCLUSIONS: Expression of NLRP3 inflammasome and IL-1β is greatly increased and mostly found in the neurons at the spinal level in SNL model, and IT gastrodin exerts a significant anti-allodynic effect in SNL model partly through suppressing the expression of NLRP3 inflammasome.
方法:鞘内(IT)导管植入和SNL用于雄性SD大鼠的给药和疼痛模型。天麻素或MCC950(NLRP3炎性体抑制剂)对机械性异常性疼痛的作用通过vonFrey试验来测量。在脊髓和背根神经节中检查了NLRP3炎性体成分和白介素1β(IL-1β)的变化以及细胞表达。
结果:NLRP3炎性体成分主要在脊髓和背根神经节的神经元中表达。NLRP3,含有caspase募集结构域(ASC)的凋亡相关斑点样蛋白的蛋白质和mRNA水平,与假动物相比,在SNL动物中caspase-1和IL-1β上调。GAS的IT给药显著减弱NLRP3炎性体的表达和SNL诱导的机械性异常性疼痛的强度。NLRP3炎性体抑制剂,MCC950也减弱了异常疼痛的强度,但效果不如GAS强和短。
结论:在SNL模型中,NLRP3炎性体和IL-1β的表达大大增加,并且主要在脊髓水平的神经元中发现,在SNL模型中,天麻素部分通过抑制NLRP3炎性体的表达发挥了显着的抗异常作用。