MMPs initiate Schwann cell-mediated MBP degradation and mechanical nociception after nerve damage.
MMPs initiate Schwann cell-mediated MBP degradation and mechanical nociception after nerve damage.
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DOI：
10.1016/j.mcn.2008.08.008
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发表时间：
2008-12
影响因子：
3.5
通讯作者：
Shubayev, Veronica I.
中科院分区：
文献类型：
--
作者：
Kobayashi, Hideo;Chattopadhyay, Sharmila;Kato, Kinshi;Dolkas, Jennifer;Kikuchi, Shin-ichi;Myers, Robert R.;Shubayev, Veronica I.
基质金属蛋白酶（MMPs）作为神经病理性疼痛的调节剂出现。由于髓鞘保护Aβ传入神经免受异位兴奋和无害机械刺激（或机械异常性疼痛）的伤害，我们分析了大鼠和MMP-9−/−小鼠L5脊神经挤压（L5 SNC）后MMP通过髓鞘蛋白降解在机械异常性疼痛发展中的作用。MMPs被证明可以促进髓鞘碱性蛋白（MBP）的选择性降解，MMP-9在L5 SNC后调节初始许旺细胞介导的MBP加工。急性和长期治疗与GM 6001（广谱MMP抑制剂）保护损伤诱导的MBP降解，半胱天冬酶介导的细胞凋亡，巨噬细胞浸润的脊神经和抑制星形胶质细胞激活脊髓。GM 6001治疗对减轻机械性异常性疼痛的效果是稳健的、即时的并且在整个L5 SNC过程中持续。总之，基质金属蛋白酶介导的启动和维持的机械伤害性感受通过雪旺细胞介导的MBP处理和支持神经炎症。
Matrix metalloproteinases (MMPs) emerge as modulators of neuropathic pain. Because myelin protects Aβ afferents from ectopic hyperexcitability and nociception from innocuous mechanical stimuli (or mechanical allodynia), we analyzed the role of MMPs in the development of mechanical allodynia through myelin protein degradation after rat and MMP-9−/− mouse L5 spinal nerve crush (L5 SNC). MMPs were shown to promote selective degradation of myelin basic protein (MBP), with MMP-9 regulating initial Schwann cell-mediated MBP processing after L5 SNC. Acute and long-term therapy with GM6001 (broad-spectrum MMP inhibitor) protected from injury-induced MBP degradation, caspase-mediated apoptosis, macrophage infiltration in the spinal nerve and inhibited astrocyte activation in the spinal cord. The effect of GM6001 therapy on attenuation of mechanical allodynia was robust, immediate and sustained through the course of L5 SNC. In conclusion, MMPs mediate the initiation and maintenance of mechanical nociception through Schwann cell-mediated MBP processing and support of neuroinflammation.
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影响因子：
3.4
作者：
Campana, WM;Myers, RR
通讯作者：
Myers, RR
影响因子：
82.9
作者：
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影响因子：
4
作者：
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影响因子：
5.3
作者：
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3
作者：
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通讯作者：
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