Upregulated natriuretic peptide B expression as a hallmark of chronic itch

Abstract – Chronic itch can arise from a variety of etiologies, ranging from dermatological conditions like eczema and psoriasis to systemic diseases such as liver disease and kidney failure. However, it remains unclear whether there are common molecular features associated with chronic itch, and whether these features are selective for chronic itch compared to chronic pain. To identify potential genes or molecular characteristics that are specifically associated with chronic itch, we examined transcriptomic data from sensory neurons collected from 3 mouse models of chronic itch and a monkey model of contact dermatitis. We compared these data to transcriptomic data from 3 mouse models of pain and clinical data from patients with neuropathic pain. Our analyses revealed that the upregulation of Nppb expression in sensory neurons is consistently associated with models of itch, but not with models of pain. Further, our cellular characterization showed that the increased expression of Nppb arises from increased cell-autonomous expression rather than the recruitment of Nppb expression in other classes of sensory neurons. Given that Nppb is a well-established itch neurotransmitter, our findings suggest that the increased expression of Nppb in sensory neurons may contribute to chronic itch. In addition, based on our results, we propose that Nppb could serve as a conserved biomarker for chronic itch.