Slack potassium channels in spinal dorsal horn neurons control neuropathic pain and acute itch.

IF 5.9 1区医学 Q1 ANESTHESIOLOGY

PAIN® Pub Date : 2024-10-08 DOI:10.1097/j.pain.0000000000003427

Fangyuan Zhou, Patrick Engel, Peter Ruth, Robert Lukowski, Achim Schmidtko, Ruirui Lu

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Abstract

Abstract: 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.

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脊髓背角神经元中的松弛钾通道控制着神经性疼痛和急性瘙痒。

摘要：钠激活钾通道 Slack（KNa1.1，Kcnt1）在调节神经元兴奋性方面起着关键作用。以往的研究发现，Slack在脊髓浅背角神经元中表达。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，我们利用脊髓背角神经元中的 Slack 被有条件消减的小鼠（Lbx1-Slack-/-小鼠），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更强的神经病理性疼痛行为，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和组胺后表现出更强的搔痒行为。此外，Lbx1-Slack-/-小鼠的背角中神经生长因子 B 受体与 Slack 共表达，鞘内注射神经生长因子 B 后，Lbx1-Slack-/-小鼠的搔抓次数增加。我们的研究提供了体内证据，证明脊髓背角神经元中表达的 Slack 可抑制神经损伤引起的异动症和各种瘙痒诱导剂引起的急性瘙痒。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

PAIN® 医学-临床神经学

CiteScore

12.50

自引率

8.10%

发文量

242

审稿时长

9 months

期刊介绍： PAIN® is the official publication of the International Association for the Study of Pain and publishes original research on the nature,mechanisms and treatment of pain.PAIN® provides a forum for the dissemination of research in the basic and clinical sciences of multidisciplinary interest.