Abstract
Pruritus is a common, but very challenging symptom with a wide diversity of underlying causes like dermatological, systemic, neurological and psychiatric diseases. In dermatology, pruritus is the most frequent symptom both in its acute and chronic form (over 6 weeks in duration). Treatment of chronic pruritus often remains challenging. Affected patients who suffer from moderate to severe pruritus have a significantly reduced quality of life. The underlying physiology of pruritus is very complex, involving a diverse network of components in the skin including resident cells such as keratinocytes and sensory neurons as well as transiently infiltrating cells such as certain immune cells. Previous research has established that there is a significant crosstalk among the stratum corneum, nerve fibers and various immune cells, such as keratinocytes, T cells, basophils, eosinophils and mast cells. In this regard, interactions between receptors on cutaneous and spinal neurons or on different immune cells play an important role in the processing of signals which are important for the transmission of pruritus. In this review, we discuss the role of various receptors involved in pruritus and inflammation, such as TRPV1 and TRPA1, IL-31RA and OSMR, TSLPR, PAR-2, NK1R, H1R and H4R, MRGPRs as well as TrkA, with a focus on interaction between nerve fibers and different immune cells. Emerging evidence shows that neuro-immune interactions play a pivotal role in mediating pruritus-associated inflammatory skin diseases such as atopic dermatitis, psoriasis or chronic spontaneous urticaria. Targeting these bidirectional neuro-immune interactions and the involved pruritus-specific receptors is likely to contribute to novel insights into the underlying pathogenesis and targeted treatment options of pruritus.
Highlights
The complex symptom of pruritus shows up in several diseases which ranges from numerous inflammatory skin diseases, metabolic disorders, liver and kidney diseases, or lymphoproliferative and myeloproliferative disorders [1]
We set our focus on transient receptor potential (TRP) channels, such as TRP vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1), the heterodimer IL-31 receptor A (IL-31RA) and oncostatin-M receptor (OSMR), thymic stromal lymphopoietin receptor (TSLPR) and different G protein-coupled receptors (GPCR)
The results demonstrated that 62, 46, and 61% of patients treated with CT327 0.05, 0.1, and 0.5%, respectively, had at least a 50% decrease in pruritus visual analog scale (VAS) in comparison to 32% on vehicle [255]
Summary
The complex symptom of pruritus shows up in several diseases which ranges from numerous inflammatory skin diseases, metabolic disorders, liver and kidney diseases, or lymphoproliferative and myeloproliferative disorders [1]. Activation of immune cells leads to the production and release of proinflammatory mediators including several cytokines, chemokines and neuropeptides that trigger neuronal pruritus response and inflammation in the skin [8, 9].
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