沉默CX3CR1对炎性痛小鼠痛阈的影响

Silencing CX3CR1 alleviates pain in a model of CFA-induced inflammatory pain in mouse

目的探讨沉默CX3CR1后炎性痛小鼠的痛阈变化。方法雄性C57BL6小鼠20只,体重30～40g,采用随机数字表法,将其随机均分为两组:沉默CX3CR1组(S组)和阴性对照组(C组)。两组均采用右侧跖底皮下注射完全氟氏佐剂50μl的方法制备小鼠炎性痛模型。S组于造模后12h鞘内注射PEI/CX3CR1-siRNA,C组鞘内注射PEI/NC-siRNA。分别于造模前(基础值)、造模后1、3、5和7d时测定右侧机械缩足阈值(MWT)、热刺激缩足潜伏期(TWL)和跖底厚度;造模后7d处死小鼠观察脊髓fractalkine及其CX3CR1的表达以及炎性介质白细胞介素(IL)-1β和肿瘤坏死因子α(TNF-α)的释放情况。结果与C组比较,S组在造模后1d起右侧MWT、TWL升高,右侧跖底厚度降低,造模后7dCX3CR1的表达降低,IL-1β、TNF-α含量减少(P<0.05)。结论 fractalkine/CX3CR1和炎性疼痛关系密切,沉默CX3CR1基因可以有效缓解炎性痛小鼠的热痛敏和机械痛敏状态。

Objective To investigate the change of pain threshold by silencing CX3CR1 using a CFA-induced inflammatory pain model in mouse. Methods Twenty male C57BL6 mice weighing 30-40 g were randomly divided into two groups （n=10）： negative control group （group C） and CX3CR1 silencing group （group S）. For both groups, inflammatory pain was induced by intraplantar injection of 50 kd of complete freund＇s adjuvant in the right hindpaw of the mice. Twelve hours after intraplantar injection, the animals in group S were injected with intratheeal PEI/CX3CRI-siRNA, and those in group C received. PEI/NC-siRNA. The right paw mechanical withdrawal threshold （MWT）, thermal withdrawal latency （TWL） and thickness of the plantar surface were measured at the time before （baseline）, 1 d, 3 d, 5 d and 7 d after modeling respectively. The expression of fractalkine, CX3CR1, IL-1β, and TNF-a were measured at 7 d after modeling. Results The mice in group S have significantly higher right side MWT and TWL value and thinner plantar surface of right hindpaw since day 1 after modeling, and lasted till day 7, compared to mice in group C. The expression levels of CX3CR1, IL-1β and TNF-α were significantly lower at 7 d after modeling in group S than in group C（P〈0.05）. Conclusion Fractalkine/CX3CR1 are closely related to inflammatory pain. Silencing CX3CR1 can effectively attenuate the thermal hyperalgesia and mechanical hyperalgesia in a mouse model of CFA-induced inflammatory pain.