Advances in Understanding the Initial Steps of Pruritoceptive Itch: How the Itch Hits the Switch

Abstract

Pruritoceptive (dermal) itch was long considered an accompanying symptom of diseases, a side effect of drug applications, or a temporary sensation induced by invading pruritogens, as produced by the stinging nettle. Due to extensive research in recent years, it was possible to provide detailed insights into the mechanism of itch mediation and modulation. Hence, it became apparent that pruritus is a complex symptom or disease in itself, which requires particular attention to improve patients’ health. Here, we summarize recent findings in pruritoceptive itch, including how this sensation is triggered and modulated by diverse endogenous and exogenous pruritogens and their receptors. A differentiation between mediating pruritogen and modulating pruritogen seems to be of great advantage to understand and decipher the molecular mechanism of itch perception. Only a comprehensive view on itch sensation will provide a solid basis for targeting this long-neglected adverse sensation accompanying numerous diseases and many drug side effects. Finally, we identify critical aspects of itch perception that require future investigation.

Interleukin-31 Signaling Bridges the Gap Between Immune Cells, the Nervous System and Epithelial Tissues

“…Thus, next to the direct engagement of peripheral sensory neurons, IL-31 may sustain pruritus via keratinocyte activation and the release of other pruritus mediators ( 58 – 60 ). Notably, besides epidermal keratinocytes, bronchial and gut epithelial cells have been shown to be a target of IL-31 ( 61 , 62 ).…”

SH-29 and SK-119 Attenuates Air-Pollution Induced Damage by Activating Nrf2 in HaCaT Cells

“…Indeed, the European health agency still considers air pollution as the largest environmental health risk, ultimately causing cardiovascular and respiratory diseases that might lead to premature deaths [ 2 , 3 , 4 ]. Environmental pollutants such as polycyclic aromatic hydrocarbons, volatile organic compounds, heavy metals, ozone (O 3 ), cigarette smoke, and particulate matter (PM) were repeatedly linked to respiratory and systemic disorders as well as an increase in the prevalence of cutaneous inflammatory diseases [ 5 , 6 , 7 ]. For instance, PM in ambient air is strongly related to the progression of atopic dermatitis in children.…”

Connections between Immune-Derived Mediators and Sensory Nerves for Itch Sensation

“…Thymic stromal lymphopoietin (TSLP) is a IL-7 like cytokine belonging to the IL-2 cytokine family [110,141]. It is primarily produced by epithelial cells, including keratinocytes, fibroblasts and stromal cells, as well as by DCs, mast cells, and basophils [110,142].…”