Amaya Fumimasa, Wang Haibin, Costigan Michael, Allchorne Andrew J, Hatcher Jon P, Egerton Julie, Stean Tania, Morisset Valerie, Grose David, Gunthorpe Martin J, Chessell Iain P, Tate Simon, Green Paula J, Woolf Clifford J
Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
J Neurosci. 2006 Dec 13;26(50):12852-60. doi: 10.1523/JNEUROSCI.4015-06.2006.
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. Na(v)1.9 is present in nociceptor sensory neurons that express TRPV1, bradykinin B2, and purinergic P2X3 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 Na(v)1.9. Pain hypersensitivity elicited by intraplantar administration of prostaglandin E2, bradykinin, interleukin-1beta, capsaicin, and P2X3 and P2Y receptor agonists, but not NGF, is either reduced or absent in Na(v)1.9-/- 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. Na(v)1.9 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.
我们使用了一种小鼠，其SCN11A（电压门控钠通道，XI型，α）基因的外显子4、5和6被删除，该基因编码电压门控钠通道Na(v)1.9，以评估其对疼痛的作用。Na(v)1.9存在于表达TRPV1、缓激肽B2和嘌呤能P2X3受体的伤害性感受器感觉神经元中。在Na(v)1.9基因敲除小鼠中，非失活的持续性河豚毒素抗性钠TTXr-Per电流缺失，而TTXr-Slow电流不变。TTXs电流不受Na(v)1.9突变的影响。足底注射前列腺素E2、缓激肽、白细胞介素-1β、辣椒素以及P2X3和P2Y受体激动剂所引发的疼痛超敏反应（但NGF引发的超敏反应除外）在Na(v)1.9基因敲除小鼠中要么减轻要么不存在，而基础热痛和机械痛敏感性未改变。外周炎症（足底注射完全弗氏佐剂）所产生的热超敏反应（而非机械超敏反应）在无效等位基因突变小鼠中显著减弱，而在两种神经性疼痛模型中的超敏反应在Na(v)1.9基因敲除小鼠中未改变。我们得出结论，Na(v)1.9是多种炎症介质在伤害性感受器外周终末产生超敏反应的效应器，因此在介导外周敏化中起关键作用。
