Role of spinal microglia in visceral hyperalgesia and NK1R up-regulation in a rat model of chronic stress.
Role of spinal microglia in visceral hyperalgesia and NK1R up-regulation in a rat model of chronic stress.
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DOI：
10.1053/j.gastro.2008.12.044
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发表时间：
2009-04
期刊：
影响因子：
29.4
通讯作者：
Mayer EA
中科院分区：
文献类型：
--
作者：
Bradesi S;Svensson CI;Steinauer J;Pothoulakis C;Yaksh TL;Mayer EA
慢性心理压力与内脏痛觉过敏和脊髓 NK1 受体 (NK1R) 表达增加有关。我们的目的是确定脊髓小胶质细胞在此过程中的作用。雄性 Wistar 大鼠每天接受 1 小时的避水 (WA) 或假应激，持续 10 天，并每天注射米诺环素、p38 抑制剂 SB203580 或盐水。通过对第 11 天收集的脊髓样本进行免疫印迹和/或免疫染色来评估激酶 p38 (P-p38)、小胶质细胞标记物 OX42、NK1R 和 IκBα 的磷酸化水平。还在注射米诺环素、SB203580 或媒介物的大鼠中测定了基线和 WA 后对结直肠扩张的内脏运动反应 (VMR)。评估了 fractalkine 对暴露于米诺环素或媒介物的大鼠 VMR 的影响。在应激大鼠中，P-p38 蛋白水平和免疫反应性增加，并与 OX42 阳性细胞和背角神经元共定位。这种增加可通过米诺环素或 SB203580 暴露而逆转。压力诱导的 NK1R 表达增加被米诺环素阻断，但 SB203580 不能阻断。 WA 诱导的 IκBα 表达下降被米诺环素和 SB203580 阻断。 WA 诱导的痛觉过敏可被米诺环素和 SB203580 IT 阻断。分形蛋白诱导的痛觉过敏被米诺环素阻断。这是首次证明应激诱导的脊髓小胶质细胞激活在内脏痛觉过敏和相关的脊髓 NK1R 上调中具有关键作用。
Chronic psychological stress is associated with visceral hyperalgesia and increased expression of spinal NK1 receptors (NK1R). We aimed to identify the role of spinal microglia in this process. Male Wistar rats were exposed to water avoidance (WA) or sham stress 1 hour each day for 10 days and given daily injections of minocycline, the p38 inhibitor SB203580, or saline. Phosphorylation levels of the kinase p38 (P-p38), the microglia marker OX42, NK1R, and IκBα were assessed by immunoblotting and/or immunostaining of spinal samples collected at Day 11. The visceromotor response (VMR) to colorectal distension at baseline and following WA were also assayed in rats given injections of minocycline, SB203580 or vehicle. The effects of fractalkine were assessed on the VMR in rats exposed to minocycline or vehicle. P-p38 protein levels and immunoreactivity were increased in stressed rats and co-localized with OX42-positive cells and neurons in the dorsal horn. This increase was reversed by minocycline or SB203580 exposure. Stress-induced increased NK1R expression was blocked by minocycline but not SB203580. WA-induced decreased IκBα expression was blocked by minocycline and SB203580. WA-induced hyperalgesia was blocked by minocycline and SB203580 IT. Fractalkine-induced hyperalgesia was blocked by minocycline. This is the first demonstration that stress-induced activation of spinal microglia has a key role in visceral hyperalgesia and associated spinal NK1R upregulation.
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影响因子：
56.9
作者：
Nimmerjahn, A;Kirchhoff, F;Helmchen, F
通讯作者：
Helmchen, F
影响因子：
2.5
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2.9
作者：
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3.3
作者：
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影响因子：
7.4
作者：
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通讯作者：
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