Functions of Slack potassium channels in neuropathic pain and itch

松弛钾通道在神经性疼痛和瘙痒中的功能

• 批准号: 440899966
• 负责人: Dr. Ruirui Lu, Ph.D.
• 金额: --
• 依托单位: Institut für Pharmakologie und Klinische Pharmazie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2020
• 资助国家: 德国
• 起止时间: 2019-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/440899966?language=en
• 关键词: Functions; Slack; potassium; channels; neuropathic

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.

神经性疼痛和慢性瘙痒影响全世界数百万人，极大地损害生活质量，并且可用药物治疗不足。累积的研究已经强调了钾（K+）通道在疼痛和瘙痒处理中的显著参与，特别是在确定感觉神经元的兴奋性中。最近鉴定的K+通道Slack（也称为Kcnt1、KNa1.1或Slo2.2）在非肽能C纤维神经元中高度表达，即在由疼痛和疼痛刺激激活的感觉神经元群体中。我们的初步工作表明，Slack选择性地控制神经病理性疼痛状态和组胺能和非组胺能瘙痒过程中的感觉输入。然而，Slack的详细功能作用和调节其活性的机制仍然知之甚少。该项目的目标是评估感觉神经元中表达的Slack对神经性疼痛和瘙痒处理的影响，评估Slack激活和调节的具体机制，并使用小鼠模型表征药理学Slack激活的影响。长期目标是找出针对Slack是否可以作为未来慢性疼痛和瘙痒药物治疗的新方法。