Genetic priming of sensory neurons in mice that overexpress PAR2 enhances allergen responsiveness
João M. Bráz, Todd Dembo, Alexandra Charruyer, Ruby Ghadially, Marlys S. Fassett, Allan I. Basbaum
Abstract
Significance Dermatitis is a major inflammatory skin condition that is associated with pruritus and affects millions of people worldwide. However, there is still little knowledge about the contribution of the cutaneous sensory neurons to the chronic disease. Here we show that chronic, but not acute, exposure to allergens/pruritogens induces robust itch in the dermatitis-prone Grhl3 PAR2/+ transgenic mouse line, in part due to profound transcriptional changes that are induced in trigeminal ganglion neurons that innervate the allergen-treated skin. Most upregulated genes were concentrated in unmyelinated primary afferents that express TRPV1, a known pruritoceptor. As comparable transcriptional changes were recorded in a second dermatitis model, we conclude that a common genetic priming program in sensory neurons contributes to dermatitis.