The voltage-gated sodium channel Nav1.9 is an effector of peripheral inflammatory pain hypersensitivity
The voltage-gated sodium channel Nav1.9 is an effector of peripheral inflammatory pain hypersensitivity
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DOI：
10.1523/jneurosci.4015-06.2006
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发表时间：
2006-12-13
影响因子：
5.3
通讯作者：
Woolf, Clifford J.
中科院分区：
文献类型：
--
作者：
Amaya, Fumimasa;Wang, Haibin;Woolf, Clifford J.
我们使用了一只缺失SCN 11 A（钠通道，电压门控，XI型，α）基因外显子4，5和6的小鼠，该基因编码电压门控钠通道Na（v）1.9，以评估其对疼痛的贡献。Nav1.9存在于表达TRPV 1、缓激肽B-2和嘌呤能P2 X（3）受体的伤害感受器感觉神经元中。在Na（v）1.9（-/-）小鼠中，不存在非失活的持续性河豚毒素抗性钠TTXr-Per电流，而TTXr-Slow电流不变。TTXs电流不受Nav1.9突变的影响。足底注射前列腺素E-2、缓激肽、白细胞介素-1 β、辣椒素、P2 X（3）和P2 Y受体激动剂引起的疼痛超敏反应，在Nav1.9（-/-）小鼠中减少或不存在，而基础的热和机械疼痛敏感性不变。在无效等位基因突变小鼠中，由外周炎症（足底内完全弗氏佐剂）产生的热超敏反应（而非机械超敏反应）显著减少，而在Na（v）1.9（-/-）小鼠中，两种神经性疼痛模型中的超敏反应无变化。我们得出结论，Nav1.9是多种炎症介质对伤害感受器外周末梢产生的超敏反应的效应物，因此在介导外周敏化中起关键作用。
We used a mouse with deletion of exons 4, 5, and 6 of the SCN11A ( sodium channel, voltage-gated, type XI, alpha) gene that encodes the voltage-gated sodium channel Na(v)1.9 to assess its contribution to pain. Nav1.9 is present in nociceptor sensory neurons that express TRPV1, bradykinin B-2, and purinergic P2X(3) receptors. In Na(v)1.9(-/-) mice, the non-inactivating persistent tetrodotoxin-resistant sodium TTXr-Per current is absent, whereas TTXr-Slow is unchanged. TTXs currents are unaffected by the mutation of Nav1.9. Pain hypersensitivity elicited by intraplantar administration of prostaglandin E-2, bradykinin, interleukin-1 beta, capsaicin, and P2X(3) and P2Y receptor agonists, but not NGF, is either reduced or absent in Nav1.9(-/-) mice, whereas basal thermal and mechanical pain sensitivity is unchanged. Thermal, but not mechanical, hypersensitivity produced by peripheral inflammation (intraplanatar complete Freund's adjuvant) is substantially diminished in the null allele mutant mice, whereas hypersensitivity in two neuropathic pain models is unchanged in the Na(v)1.9(-/-) mice. Nav1.9 is, we conclude, an effector of the hypersensitivity produced by multiple inflammatory mediators on nociceptor peripheral terminals and therefore plays a key role in mediating peripheral sensitization.