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

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 Gi-DREADD-mediated inactivation of these Phox2a-keratinocytes completely reverses the skin lesions, while inducible tTA activation of the keratinocytes initiates the condition. Notably, ablation of TRPV1-expressi..., , # Data from: Keratinocyte-TRPV1 sensory neuron interactions in a genetically controllable mouse model of chronic neuropathic itch

Dataset DOI: [10.5061/dryad.tdz08kq9s](10.5061/dryad.tdz08kq9s)

## Description of the data

Various behavioral quantifications, histological quantifications, and images to support the associated PNAS paper.

### Files and variables

#### File: qPCR\_k14.prism

**Description:** In tamoxifen-injected KRT14-CreER; Ai162 mice and littermate Cre negative controls, a ventral 2x2 cm patch of skin was harvested. The epidermis was separated from the whole skin by incubating in Trypsin-EDTA 0.15% for 45 minutes. Isolated cells from the epidermis and whole mRNA were extracted using a RNeasy Mini kit from Qiagen after which was reverse transcribed into cDNA using Superscript IV (Thermo Fisher Cat # 18091200). qPCR analyses were carried out with gene specific primers and fluorescently labeled Taqman probes (ThermoFisher Scientific) for Tslp (Mm01157588_m1), Il33 (Mm0050...,