Changes of voltage-gated sodium channels in sensory nerve regeneration and neuropathic pain models
Changes of voltage-gated sodium channels in sensory nerve regeneration and neuropathic pain models
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DOI：
10.3233/rnn-140444
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发表时间：
2015-01-01
影响因子：
2.8
通讯作者：
Navarro, Xavier
中科院分区：
文献类型：
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作者：
Casals-Diaz, Laura;Casas, Caty;Navarro, Xavier
目的：探讨神经损伤后电压门控钠通道(VGSCs)α亚基表达的变化及其与神经病理性疼痛发生的关系。方法：采用大鼠坐骨神经挤压损伤再生模型(CRUSH)和备用神经损伤(SNI)模型。直到伤后3个月进行热痛和机械痛阈值的测量。实时荧光定量聚合酶链式反应和免疫组织化学方法检测VGSCα亚基在DRG中的表达。结果：两种神经损伤后7dpi的VGSC表达变化相似，Nav1.3表达上调，Nav1.7、Nav1.8和Nav1.9表达下调。这些变化持续到28天，在SNI中仍存在痛觉过敏，但在CRUSH大鼠中则不存在。在90天时，CRUSH组所有被分析的α亚基的mRNA表达都恢复到基础水平。然而，SNI大鼠仍然表现出VGSCs表达的改变和神经病理性疼痛反应。免疫组织化学染色显示，NAV1.8和NA1.9广泛表达于背根神经节IB4阳性神经元，与痛觉加工有关。各α亚单位和IB4共表达的神经元数量也受到损伤的影响，损伤后更为明显。结论：VGSCs表达的变化与大鼠神经病理性疼痛行为平行发生，但在后期似乎更多地与感觉神经的退变和再生过程有关。
Purpose: The present study was conducted to determine changes in the expression of voltage-gated sodium channels (VGSCs) alpha-subunits after nerve injury and their relation with development of neuropathic pain.Methods: We used the crush injury model of regeneration of the sciatic nerve (Crush) and the spared nerve injury (SNI) model of neuropathic pain in the rat. Measurements of thermal and mechanical pain thresholds were performed until 3 months after injury. Real-time PCR and immunohistochemistry of VGSC alpha-subunits were used to evaluate the mRNA and protein expression in the DRG.Results: Both nerve injuries induced similar alterations in the VGSCs expression at 7 dpi, with upregulation of Nav1.3, and downregulation of Nav1.7, Nav1.8 and Nav1.9. These changes persisted until 28 days, when hyperalgesia was still present in SNI but not in Crush rats. At 90 days, mRNA expression of all analyzed alpha-subunits returned to basal levels in the Crush group. However, SNI rats still showed altered expression of VGSCs, and neuropathic pain responses. Immunohistochemical staining revealed that Nav1.8 and Nav1.9 were widely expressed in IB4-positive neurons of the DRG, relevant in pain processing. The population of neurons coexpressing each alpha-subunit and IB4 was also affected by the injury, more markedly after the Crush.Conclusion: Shifts in VGSCs expression occur in parallel to neuropathic pain behavior in rats early after injury, while at later times they appear to be more related to sensory nerve degeneration and regeneration processes.