背根神经节MMP-9在瑞芬太尼引起的大鼠痛觉过敏中的作用

MMP-9 in Dorsal Root Ganglion Contributes to Remifentanil-induced Hyperalgesia in Rats

【目的】观察瑞芬太尼是否引起大鼠痛觉过敏并导致基质金属蛋白酶9(MMP-9)在其背根神经节(DRG)中发生改变。【方法】成年雄性SD大鼠静脉输注瑞芬太尼建立痛觉过敏模型,分别利用von Frey及Hargreaves法检测瑞芬太尼输注后2 h至5 d的机械及热刺激撤足阈值变化。为观察MMP-9在瑞芬太尼诱导的痛觉过敏中的作用,在静脉输注瑞芬太尼前30 min预先鞘内注射MMP-9抑制剂。采用免疫荧光和免疫印迹方法观察背根神经节(DRG)中MMP-9的表达变化。【结果】静脉输注瑞芬太尼后,大鼠的痛觉阈值明显下降(P<0.01),说明痛觉过敏形成,且痛觉过敏的程度及持续时间与瑞芬太尼输注时间有关;而预先鞘内注射MMP-9抑制剂可缓解瑞芬太尼输注引起的痛觉过敏。免疫荧光及免疫印迹结果显示瑞芬太尼输注可上调大鼠DRG中MMP-9的表达(P<0.01)。【结论】持续输注瑞芬太尼可诱导形成痛觉过敏,使DRG中MMP-9表达增加,这可能是瑞芬太尼导致痛觉过敏的机制之一。

【Objective】 To investigate the expression of matrix metalloproteases 9（MMP-9） in dorsal root ganglion（DRG） in remifentanil-induced hyperalgesia. 【Methods】 Hyperalgesia was induced by intravenous infusion of remifentanil 4 μg / kg / min for 0.5~ 2 h and MMP-9 inhibitor was intrathecally administered 30 min before remifentanil infusion. Nociception was assessed using Von Frey test and Hargreaves methods after remifentanil infusion from the 2nd hour to the 5th day and the expression of MMP-9 in dorsal root ganglion（DRG）was observed with immunohistochemistry and Western blot analysis. 【Results】 Intravenous infusion of remifentanil led to significant reduction of sensory threshold and pretreatment with MMP-9 inhibitor could attenuate hyperalgesia induced by remifentanil. Immunohistochemistry and Western blot results showed that MMP-9 expression was significantly upregulated in the DRG in remifentanil hyperalgesia rats. 【Conclusions】 High MMP-9 expression in DRG could be suggestive of a underlying mechanism of hyperalgesia induced by remifentanil.