Differential expression of tetrodotoxin-resistant sodium channels NaV1.8 and NaV1.9 in normal and inflamed rats

Differential expression of tetrodotoxin-resistant sodium channels NaV1.8 and NaV1.9 in normal and inflamed rats
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DOI:
10.1016/j.neulet.2003.10.023
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发表时间:
2004-01-23
影响因子:
2.5
通讯作者:
Carlton, SM
Carlton, SM
中科院分区:
医学4区
文献类型:
--
作者:
Coggeshall, RE;Tate, S;Carlton, SM

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为了了解主要传入纤维外周敏化的机制,我们研究了正常和炎症大鼠后肢指神经轴突上Na(v)1.8 (SNS)和Na(v)1.9 (SNS2)抗河蟹毒素Na+通道亚基的存在。在正常动物中,14.3%的无髓细胞轴突和10.7%的有髓细胞轴突标记为Na(v)1.8亚基。这些百分比在48小时炎症动物中显著增加,无髓和有髓轴突分别为22.0%(增加1.5倍)和57.5%(增加6倍)。在正常动物中,Na(v)1.9标记9.9%的无髓轴突和2.1%的有髓轴突,炎症后,Na(v)1.9标记的无髓轴突比例显著下降至3.0%,标记的有髓轴突比例没有变化。这些数据表明,Na(v)1.8和Na(v)1.9亚基在正常动物中被转运到外周,并在炎症期间受到差异调节。髓鞘轴突Na(v)1.8表达的大量增加表明这些可能有助于外周致敏和炎症性痛觉过敏。2003爱思唯尔爱尔兰有限公司版权所有。
In an attempt to understand mechanisms underlying peripheral sensitization of primary afferent fibers, we investigated the presence of the tetrodotoxin-resistant Na+ channel subunits Na(v)1.8 (SNS) and Na(v)1.9 (SNS2) on axons in digital nerves of normal and inflamed rat hindpaws. In normal animals, 14.3% of the unmyelinated and 10.7% of the myelinated axons labeled for the Na(v)1.8 subunit. These percentages significantly increased in 48 h inflamed animals to 22.0% (1.5-fold increase) and 57.5% (6-fold increase) for unmyelinated and myelinated axons, respectively. In normal animals, Na(v)1.9 labeled 9.9% of the unmyelinated and 2.1% of the myelinated axons and following inflammation, the proportion of Na(v)1.9-labeled unmyelinated axons significantly decreased to 3.0% with no change in the proportion of labeled myelinated axons. These data indicate that Na(v)1.8 and Na(v)1.9 subunits are transported to the periphery in normal animals and are differentially regulated during inflammation. The massive increase in Na(v)1.8 expression in myelinated axons suggests that these may contribute to peripheral sensitization and inflammatory hyperalgesia. (C) 2003 Elsevier Ireland Ltd. All rights reserved.