Src-family kinases activation in spinal microglia contributes to central sensitization and chronic pain after lumbar disc herniation.
Src-family kinases activation in spinal microglia contributes to central sensitization and chronic pain after lumbar disc herniation.
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脊髓小胶质细胞中 Src 家族激酶的激活导致腰椎间盘突出症后中枢敏化和慢性疼痛
DOI：
10.1177/1744806917733637
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发表时间：
2017-01
期刊：
影响因子：
3.3
通讯作者：
Zhong Y
中科院分区：
文献类型：
--
作者：
Huang Y;Li Y;Zhong X;Hu Y;Liu P;Zhao Y;Deng Z;Liu X;Liu S;Zhong Y
腰椎间盘突出症是神经根性疼痛的主要原因，但其潜在机制仍不清楚。脊髓中 src 家族激酶的激活与神经损伤、炎症和癌症引起的慢性疼痛的发展有关。在本研究中，研究了 src 家族激酶激活在腰椎间盘突出引起的根性疼痛中的作用。通过将尾部采集的自体髓核植入大鼠腰椎4/5脊神经根来诱导腰椎间盘突出症。行为测试和电生理数据表明，髓核植入可引起持续性机械性异常性疼痛和热痛觉过敏，并提高脊髓背角突触传递的效率，而脊髓背角是痛觉中枢敏化的基础。 Western blotting和免疫组化染色显示，磷酸化src家族激酶的表达上调主要在髓核大鼠脊髓小胶质细胞中。鞘内递送 src 家族激酶抑制剂 PP2 可减轻疼痛行为，降低脊髓突触传递效率，并减少磷酸化 src 家族激酶的表达。此外，我们发现髓核大鼠脊髓背角中离子钙结合接头分子1（小胶质细胞的标志物）、肿瘤坏死因子-α、白细胞介素1 -β的表达增加。 PP2的治疗效果可能与其减少这些因子表达的能力有关。这些发现表明，中枢敏化与腰椎间盘突出症引起的神经根性疼痛有关。 src家族激酶介导的炎症反应可能是腰椎间盘突出症后中枢敏化和慢性疼痛的原因。
Lumbar disc herniation is a major cause of radicular pain, but the underlying mechanisms remain largely unknown. Spinal activation of src-family kinases are involved in the development of chronic pain from nerve injury, inflammation, and cancer. In the present study, the role of src-family kinases activation in lumbar disc herniation-induced radicular pain was investigated. Lumbar disc herniation was induced by implantation of autologous nucleus pulposus, harvest from tail, in lumbar 4/5 spinal nerve roots of rat. Behavior test and electrophysiologic data showed that nucleus pulposus implantation induced persistent mechanical allodynia and thermal hyperalgesia and increased efficiency of synaptic transmission in spinal dorsal horn which underlies central sensitization of pain sensation. Western blotting and immunohistochemistry staining revealed that the expression of phosphorylated src-family kinases was upregulated mainly in spinal microglia of rats with nucleus pulposus. Intrathecal delivery of src-family kinases inhibitor PP2 alleviated pain behaviors, decreased efficiency of spinal synaptic transmission, and reduced phosphorylated src-family kinases expression. Furthermore, we found that the expression of ionized calcium-binding adapter molecule 1 (marker of microglia), tumor necrosis factor-α, interleukin 1 -β in spinal dorsal horn was increased in rats with nucleus pulposus. Therapeutic effect of PP2 may be related to its capacity in reducing the expression of these factors. These findings suggested that central sensitization was involved in radicular pain from lumbar disc herniation; src-family kinases-mediated inflammatory response may be responsible for central sensitization and chronic pain after lumbar disc herniation.
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影响因子：
3
作者：
Freeman, Brian J. C.;Ludbrook, Guy L.;Gorman, James R.
通讯作者：
Gorman, James R.
影响因子：
4.2
作者：
Huang, Yangliang;Zang, Ying;Zhong, Yi
通讯作者：
Zhong, Yi
影响因子：
8.8
作者：
Liu, Zhi-hua;Miao, Gui-shen;Sun, Tao
通讯作者：
Sun, Tao
在非压迫性腰椎间盘突出症大鼠模型中，脂氧素 A4 可能通过抑制脊髓 ERK、JNK 和 NF-κB/p65 和细胞因子信号（但不是 p38）来减轻神经根痛
影响因子：
3.3
作者：
Miao, G. -S;Liu, Z. -H;Sun, T.
通讯作者：
Sun, T.
影响因子：
2.8
作者：
Mukai, Michiaki;Sakuma, Yoshihiro;Ohtori, Seiji
通讯作者：
Ohtori, Seiji