Specific functions of sodium-activated potassium channels in pain and itch

• Applicant: Ruirui Lu, Ph.D.
• Subject Area: Pharmacology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 546368299

Chronic pain and itch affect millions of individuals worldwide, greatly impair their quality of life, and are inadequately treated with available drugs. Accumulating research has highlighted a prominent involvement of potassium channels in pain and itch processing, particularly in determining the excitability of sensory neurons and spinal dorsal horn neurons. Recently, two distinct sodium-activated potassium channels, Slack (also termed KNa1.1 or Slo2.2; gene Kcnt1) and Slick (also termed KNa1.2, or Slo2.1; gene Kcnt2) have attracted significant interest as regulators of pain and itch. In a series of experiments, we explored that Slack, which is highly expressed in non-peptidergic nociceptors, modulates non-histaminergic itch, whereas Slick expressed in A delta fiber nociceptors and spinal dorsal horn neurons contributes to heat sensation and neuropathic pain processing. However, the detailed functional roles of Slack and Slick remain poorly understood. The goal of the project is to investigate the impact of Slack expressed in sensory neurons for histamine-independent itch, and to assess specific mechanisms of Slick activation in heat sensation and neuropathic pain. The long-term goal is to find out whether targeting Slack and/or Slick could serve as a new approach for the pharmacological treatment of chronic pain and itch in the future.

• DFG Programme: Research Grants