Keratinocyte-TRPV1 sensory neuron interactions in a genetically controllable mouse model of chronic neuropathic itch.

ABSTRACT: Our understanding of neural circuits that respond to skin dysfunction, triggering itch, and pathophysiological scratching remains incomplete. Here, we describe a profound chronic itch phenotype in transgenic mice expressing the tetracycline transactivator (tTA) gene within the Phox2a lineage. Phox2a; tTA mice exhibit intense, localized scratching and regional skin lesions, controllable by the tTA inhibitor, doxycycline. As gabapentin and the kappa opioid receptor agonist, nalfurafine, but not morphine, significantly reduce scratching, this phenotype has a pharmacological profile of neuropathic pruritus. Importantly, the Phox2a; tTA expression occurs in a spatially restricted population of skin keratinocytes that overlaps precisely with the skin area that is scratched. Localized G_i

SUBMITTER: Crowther AJ 

PROVIDER: S-EPMC12184494 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature