Distinct Nav1.7-dependent pain sensations require different sets of sensory and sympathetic neurons.
Distinct Nav1.7-dependent pain sensations require different sets of sensory and sympathetic neurons.
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DOI：
10.1038/ncomms1795
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发表时间：
2012-04-24
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
人类急性和炎性疼痛需要电压门控钠通道Nav1.7的表达，但其对神经性疼痛的意义尚不清楚。在这里，我们表明，Nav1.7表达在不同的小鼠感觉和交感神经元的基础不同类型的疼痛感觉。使用Advillin-Cre消除所有感觉神经元中的Nav1.7基因（SCN 9A）表达消除了机械性疼痛、炎性疼痛和对热的反射性退缩反应。相反，当SCN 9A仅在Nav1.8阳性伤害感受器中缺失时，热诱发的疼痛保留。令人惊讶的是，当所有感觉神经元中的SCN 9A被删除时，对热板测试的反应以及神经性疼痛不受影响。然而，在感觉和交感神经元中删除SCN 9A会消除这些疼痛感觉，并重现在具有SCN 9A功能丧失突变的人类中观察到的无痛表型。这些观察结果表明Nav1.7在神经病理性疼痛的交感神经元中的重要作用，并提供了可能的见解，了解功能获得Nav1.7依赖性疼痛条件的机制。钠通道Nav1.7是人类急性疼痛所必需的，但其在慢性神经性疼痛中的作用尚不清楚。Minett及其同事表明，Nav1.7在交感神经元而不是感觉神经元中的特异性表达是损伤后慢性神经性疼痛发展所必需的。
Human acute and inflammatory pain requires the expression of voltage-gated sodium channel Nav1.7 but its significance for neuropathic pain is unknown. Here we show that Nav1.7 expression in different sets of mouse sensory and sympathetic neurons underlies distinct types of pain sensation. Ablating Nav1.7 gene (SCN9A) expression in all sensory neurons using Advillin-Cre abolishes mechanical pain, inflammatory pain and reflex withdrawal responses to heat. In contrast, heat-evoked pain is retained when SCN9A is deleted only in Nav1.8-positive nociceptors. Surprisingly, responses to the hotplate test, as well as neuropathic pain, are unaffected when SCN9A is deleted in all sensory neurons. However, deleting SCN9A in both sensory and sympathetic neurons abolishes these pain sensations and recapitulates the pain-free phenotype seen in humans with SCN9A loss-of-function mutations. These observations demonstrate an important role for Nav1.7 in sympathetic neurons in neuropathic pain, and provide possible insights into the mechanisms that underlie gain-of-function Nav1.7-dependent pain conditions. Sodium channel Nav1.7 is essential for acute human pain but its role in chronic neuropathic pain is unclear. Minett and colleagues show that Nav1.7 expression specifically in sympathetic neurons, rather than sensory neurons, is required for the development of chronic neuropathic pain after injury.
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DOI：
10.1073/pnas.1013602108
发表时间：
2011-04-05
影响因子：
11.1
作者：
Lagerstrom, Malin C.;Rogoz, Katarzyna;Kullander, Klas
通讯作者：
Kullander, Klas
DOI：
10.3344/kjp.2010.23.1.55
发表时间：
2010-03
期刊：
The Korean journal of pain
影响因子：
--
作者：
Bang YJ;Yeo JS;Kim SO;Park YH
通讯作者：
Park YH
DOI：
10.1016/1056-8719(94)00077-h
发表时间：
1995-09-01
影响因子：
1.9
作者：
LANGERMAN, L;ZAKOWSKI, MI;GRANT, GJ
通讯作者：
GRANT, GJ
影响因子：
3.3
作者：
Ghelardini, C.;Desaphy, J. -F.;Camerino, D. Conte
通讯作者：
Camerino, D. Conte
影响因子：
16.2
作者：
Lagerstrom, Malin C.;Rogoz, Katarzyna;Abrahamsen, Bjarke;Persson, Emma;Reinius, Bjorn;Nordenankar, Karin;Olund, Caroline;Smith, Casey;Mendez, Jose Alfredo;Chen, Zhou-Feng;Wood, John N.;Wallen-Mackenzie, Asa;Kullander, Klas
通讯作者：
Kullander, Klas