Functions of Slack potassium channels in neuropathic pain and itch

神经性疼痛和慢性瘙痒影响着全世界数以百万计的人，极大地损害了生活质量，并且用现有的药物治疗不足。越来越多的研究强调了钾（K+）通道在疼痛和瘙痒过程中的重要参与，特别是在决定感觉神经元的兴奋性方面。最近发现的K+通道Slack（也称为Kcnt1， KNa1.1或Slo2.2）在非肽能性C纤维神经元中高度表达，即在疼痛和瘙痒刺激激活的感觉神经元群体中。我们的初步工作表明，Slack选择性地控制神经性疼痛状态以及组胺能和非组胺能瘙痒过程中的感觉输入。然而，Slack的详细功能角色和调节其活动的机制仍然知之甚少。该项目的目标是评估Slack在感觉神经元中表达对神经性疼痛和瘙痒的影响，评估Slack激活和调节的具体机制，并利用小鼠模型表征Slack药理激活的效果。长期目标是发现针对Slack是否可以作为未来慢性疼痛和瘙痒药物治疗的新方法。

Neuropathic pain and chronic itch affect millions of individuals worldwide, greatly impair quality of life, and are inadequately treated with available drugs. Accumulating research has highlighted a prominent involvement of potassium (K+) channels in pain and itch processing, particularly in determining the excitability of sensory neurons. The recently identified K+ channel Slack (also termed Kcnt1, KNa1.1 or Slo2.2) is highly expressed in non-peptidergic C fiber neurons, i.e. in a population of sensory neurons activated by painful and pruritic stimuli. Our preliminary work revealed that Slack selectively controls the sensory input in neuropathic pain states and during the processing of histaminergic and non-histaminergic itch. However, the detailed functional role of Slack and the mechanisms regulating its activity in remain poorly understood. The goal of the project is to evaluate the impact of Slack expressed in sensory neurons for the processing of neuropathic pain and itch, to assess specific mechanisms of Slack activation and modulation, and to characterize the effects of pharmacological Slack activation using mouse models. The long-term goal is to find out whether targeting Slack could serve as a new approach for pharmacological treatment of chronic pain and itch in future.