Engaging pain fibers after a spinal cord injury fosters hemorrhage and expands the area of secondary injury.
Engaging pain fibers after a spinal cord injury fosters hemorrhage and expands the area of secondary injury.
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DOI：
10.1016/j.expneurol.2018.09.018
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发表时间：
2019-01
影响因子：
5.3
通讯作者：
Grau JW
中科院分区：
文献类型：
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作者：
Turtle JD;Henwood MK;Strain MM;Huang YJ;Miranda RC;Grau JW
在人类中，脊髓损伤（SCI）通常伴有额外的组织损伤（多发损伤），可累及疼痛（伤害）纤维。先前的研究表明，这种伤害性输入可以扩大组织损伤（继发性损伤）的面积，破坏行为恢复，并促进慢性疼痛的发展。本研究表明，大鼠下胸挫伤后一天给予伤害性输入，可增强损伤部位红细胞的浸润，产生出血区域，扩大继发性损伤。外周伤害性纤维在损伤24小时后通过电刺激（电击）或刺激性辣椒素的强度参与无髓鞘疼痛纤维(C)。趋同免疫印迹和氰高铁血红蛋白比色分析显示，两种形式的刺激都增加了损伤部位的血红蛋白浓度，并在刺激后3-24小时观察到强烈的影响。组织病理学证实，休克治疗增加了出血面积和红细胞的浸润。脊髓损伤可通过干扰神经血管内皮细胞中的磺酰脲受体1 （SUR1）瞬时受体电位美拉他汀4 （TRPM4）通道复合物导致出血，从而导致细胞死亡和毛细血管断裂。组织病理学证实出血区毛细血管断裂。SUR1-TRPM4复合物的共免疫沉淀表明，它在有害刺激下被上调。休克性出血与运动能力的急性中断有关。这些结果表明，有害刺激损害了长期恢复，因为它扩大了血脊髓屏障（BSCB）的破坏和红细胞的浸润，从而扩大了继发性损伤的面积。
In humans, spinal cord injury (SCI) is often accompanied by additional tissue damage (polytrauma) that can engage pain (nociceptive) fibers. Prior work has shown that this nociceptive input can expand the area of tissue damage (secondary injury), undermine behavioral recovery, and enhance the development of chronic pain. Here, it is shown that nociceptive input given a day after a lower thoracic contusion injury in rats enhances the infiltration of red blood cells at the site of injury, producing an area of hemorrhage that expands secondary injury. Peripheral nociceptive fibers were engaged 24 h after injury by means of electrical stimulation (shock) applied at an intensity that engages unmyelinated pain (C) fibers or through the application of the irritant capsaicin. Convergent western immunoblot and cyanmethemoglobin colorimetric assays showed that both forms of stimulation increased the concentration of hemoglobin at the site of injury, with a robust effect observed 3–24 h after stimulation. Histopathology confirmed that shock treatment increased the area of hemorrhage and the infiltration of red blood cells. SCI can lead to hemorrhage by engaging the sulfonylurea receptor 1 (SUR1) transient receptor potential melastatin 4 (TRPM4) channel complex in neurovascular endothelial cells, which leads to cell death and capillary fragmentation. Histopathology confirmed that areas of hemorrhage showed capillary fragmentation. Co-immunoprecipitation of the SUR1-TRPM4 complex showed that it was up-regulated by noxious stimulation. Shock-induced hemorrhage was associated with an acute disruption in locomotor performance. These results imply that noxious stimulation impairs long-term recovery because it amplifies the breakdown of the blood spinal cord barrier (BSCB) and the infiltration of red blood cells, which expands the area of secondary injury.
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