Implication of microglia activation and CSF-1/CSF-1Rpathway in lumbar disc degeneration-related back pain.
Implication of microglia activation and CSF-1/CSF-1Rpathway in lumbar disc degeneration-related back pain.
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小胶质细胞激活和 CSF-1/CSF-1R 通路在腰椎间盘退变相关背痛中的意义。
DOI：
10.1177/1744806918811238
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发表时间：
2018-01
期刊：
影响因子：
3.3
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Yang G;Chen L;Gao Z;Wang Y
背部疼痛是常见的和昂贵的。虽然腰椎间盘退变一直被认为是背痛的主要原因，但椎间盘退变如何导致背痛仍不清楚。最近的研究观察到椎间盘退变后脊髓中的小胶质细胞活化，表明活化的小胶质细胞可能参与椎间盘源性背痛。为了确定小胶质细胞激活是否参与椎间盘退变诱导的背痛，我们使用了一种改良的椎间盘穿刺诱导的退变相关背痛小鼠模型来检查脊髓小胶质细胞的变化，并研究小胶质细胞激活与椎间盘源性背痛之间的潜在联系。在这项研究中，46只CX 3CR 1GFP/+雄性小鼠被用于实验组和假手术组。实验组采用改良的后外侧腹膜后入路暴露L3/L4椎间盘，诱导穿刺。行为测试，包括握力和身体功能，用于测量术前和术后的背痛。术后1 ~ 4周取L3背根神经节和腰髓，用不同抗体进行免疫荧光染色。通过共聚焦显微镜获得显微照片，并使用Imaris分析小胶质细胞的形态测量。穿刺的椎间盘进行性退变，椎间盘退变的小鼠表现出握力和身体功能受损。与对照组小鼠相比，椎间盘穿刺动物腰髓中的小胶质细胞数量显著增加。此外，在椎间盘损伤小鼠中，积聚的小胶质细胞表现出更大的索马尺寸和更少的分支。免疫荧光显示集落刺激因子1，一种促进小胶质细胞再增殖的细胞因子，在L3背根神经节中显著增加，而其受体集落刺激因子1受体在椎间盘损伤小鼠的小胶质细胞上上调。总之，腰椎间盘穿刺导致进行性椎间盘退变，从而诱导小鼠小胶质细胞活化和背痛。增加的集落刺激因子1/集落刺激因子1受体信号转导参与椎间盘退变诱导的小胶质细胞活化和背痛。
Back pain is common and costly. Although lumbar disc degeneration has long been regarded as a major contributor to back pain, how disc degeneration leads to back pain remains unclear. Recent studies observed microglia activation in the spinal cord after disc degeneration, suggesting activated microglia may be involved in discogenic back pain. To determine whether microglia activation participates in disc degeneration-induced back pain, we used a modified disc puncture-induced degeneration-related back pain mouse model to examine the changes in spinal microglia and investigate the potential link between microglia activation and discogenic back pain. In this study, 46 CX3CR1GFP/+ male mice were used in experimental and sham groups. A modified posterolateral retroperitoneal approach was used to expose the L3/L4 disc to induce the needle puncture in the experimental group. Behavioral tests, including grip force and physical function, were used to measure back pain at pre- and postsurgery. The L3 dorsal root ganglions and lumbar spinal cord were obtained at postoperative weeks 1 to 4 followed by immunofluorescence with different antibodies. Micrographs were obtained by confocal microscopy, and morphometric measurements of microglia were analyzed using Imaris. The punctured disc underwent progressive degeneration and mice with disc degeneration showed impaired grip force and physical function. Compared to the control mice, the number of microglia in the lumbar spinal cord was significantly increased in the disc-punctured animals. Moreover, accumulated microglia exhibited larger soma size and lesser ramification in the disc-injured mice. Immunofluorescence demonstrated colony-stimulating factor 1, a cytokine that promotes microglia repopulation, was significantly increased in L3 dorsal root ganglions, whereas its receptor colony-stimulating factor 1 receptor was upregulated on microglia in the disc-injured mice. In summary, lumbar disc puncture caused progressive disc degeneration which induced microglia activation and back pain in mice. Increased colony-stimulating factor 1/colony-stimulating factor 1 receptor signaling is involved in the disc degeneration-induced microglia activation and back pain.
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影响因子：
3
作者：
Miyagi, Masayuki;Ishikawa, Tetsuhiro;Ohtori, Seiji
通讯作者：
Ohtori, Seiji
影响因子：
6.1
作者：
Chen, Chia-Hsian;Chiang, Chang-Jung;Tsai, Tung-Hu
通讯作者：
Tsai, Tung-Hu
影响因子：
3
作者：
Gruber, HE;Johnson, T;Hanley, EN
通讯作者：
Hanley, EN
影响因子：
3
作者：
Fagan, A;Moore, R;Fraser, R
通讯作者：
Fraser, R
DOI：
10.1007/978-1-84800-934-9_45
发表时间：
2009-01-01
期刊：
CLINICIAN'S PEARLS AND MYTHS IN RHEUMATOLOGY
影响因子：
--
作者：
Dixit, Rajiv K.;Schwab, Joseph H.
通讯作者：
Schwab, Joseph H.