TRESK background K+ channel deletion selectively uncovers enhanced mechanical and cold sensitivity

Changes in TRESK K + channel expression/function enhance sensory neurons excitability, but its role in somatosensory perception and nociception is poorly understood. We show that TRESK regulates the sensitivity to mechanical and cold stimuli but not the perception of heat. TRESK knockout mice nociceptive neurons present an enhanced excitability; skin nociceptive C-fibers show an increased activation by lower intensity cold or mechanical stimulation and mice lacking TRESK present mechanical and cold hypersensitivity. TRESK is also involved in osmotic pain and in early phases of formalin-induced inflammatory pain, but not in the development of mechanical and heat hyperalgesia during chronic pain. In contrast, mice lacking TRESK present cold allodynia that is not further enhanced by oxaliplatin. In summary, genetic removal of TRESK uncovers enhanced mechanical and cold sensitivity, indicating that it regulates the excitability of specific neuronal subpopulations involved in mechanosensitivity and cold-sensing, acting as a brake to prevent activation by low-intensity stimuli.