The sodium-activated potassium channel Slack (KNa1.1, Kcnt1) plays a critical role in tuning neuronal excitability. Previous studies have revealed that Slack is expressed in neurons of the superficial dorsal horn of the spinal cord. However, the precise role of Slack in spinal dorsal horn neurons is unclear. In this study, we used mice in which Slack is conditionally ablated in spinal dorsal horn neurons (Lbx1-Slack-/- mice) and analyzed their behaviors in various models of pain and itch. Lbx1-Slack-/- mice exhibited increased neuropathic pain behavior after peripheral nerve injury but normal responses in a model of inflammatory pain. Unexpectedly, Lbx1-Slack-/- mice demonstrated increased scratching after intradermal injection of chloroquine, LY344864, and histamine. Moreover, neuromedin B receptors are coexpressed with Slack in the dorsal horn, and scratching after intrathecal delivery of neuromedin B was increased in Lbx1-Slack-/- mice. Our study provides in vivo evidence that Slack expressed in spinal dorsal horn neurons inhibits nerve injury-induced allodynia and acute itch induced by various pruritogens.

中文翻译：

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脊髓背角神经元中松弛的钾通道控制神经性疼痛和急性瘙痒。


钠激活的钾通道松弛 （KNa1.1， Kcnt1） 在调节神经元兴奋性中起关键作用。以前的研究表明，Slack 在脊髓浅表背角的神经元中表达。然而，Slack 在脊髓背角神经元中的确切作用尚不清楚。在这项研究中，我们使用了在脊髓背角神经元 （Lbx1-Slack-/- 小鼠） 中条件消融 Slack 的小鼠，并分析了它们在各种疼痛和瘙痒模型中的行为。Lbx1-Slack-/-小鼠在周围神经损伤后表现出神经性疼痛行为增加，但在炎症性疼痛模型中反应正常。出乎意料的是，Lbx1-Slack-/-小鼠在皮内注射氯喹、LY344864和组胺后表现出抓挠增加。此外，神经调节素 B 受体与背角中的 Slack 共表达，并且在 Lbx1-Slack-/- 小鼠鞘内递送神经调节素 B 后搔抓增加。我们的研究提供了体内证据，表明在脊髓背角神经元中表达的 Slack 抑制了神经损伤引起的异常性疼痛和各种瘙痒原诱导的急性瘙痒。