Enhanced nonpeptidergic intraepidermal fiber density and an expanded subset of @entity503 -responsive trigeminal neurons in a XXXX model of dry skin itch.

@entity503 @entity19 @entity1324 @entity102 @entity111 @entity4543 @entity158 @entity12819 @entity7519
@entity102 are often associated with dry skin and loss of epidermal barrier integrity. In this study, repeated application of @entity1324 and @entity4543 followed by water (AEW) to the cheek skin of @entity19 produced persistent scratching behavior with no increase in @entity158 , indicating the generation of itch without @entity158 . Cheek skin immunohistochemistry showed a 64.5% increase in total epidermal innervation in AEW-treated @entity19 compared to water-treated controls. This increase was independent of scratching, because @entity19 prevented from scratching by Elizabethan collars showed similar hyperinnervation. To determine the effects of dry skin treatment on specific subsets of peripheral fibers, we examined Ret-positive, @entity12819 ( @entity12819 )-positive, and glial cell line-derived neurotrophic factor family receptor a3 ( @entity7519 )-positive intraepidermal fiber density. AEW treatment increased Ret-positive fibers but not @entity12819 -positive or @entity7519 -positive fibers, suggesting that a specific subset of nonpeptidergic fibers could contribute to dry skin itch. To test whether trigeminal ganglion neurons innervating the cheek exhibited altered excitability after AEW treatment, primary cultures of retrogradely labeled neurons were examined using whole-cell patch clamp electrophysiology. AEW treatment produced no differences in measures of excitability compared to water-treated controls. In contrast, a significantly higher proportion of trigeminal ganglion neurons was responsive to the nonhistaminergic pruritogen @entity503 after AEW treatment. We conclude that nonpeptidergic, Ret-positive fibers and @entity503 -sensitive neurons may contribute to dry skin @entity111 . PERSPECTIVE: This study examines the underlying neurobiological mechanisms of persistent dry skin itch. Our results indicate that nonpeptidergic epidermal hyperinnervation and nonhistaminergic pruritic receptors are potential targets for chronic @entity111 .
