Functions of Slack potassium channels in neuropathic pain and itch

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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.