BACKGROUND: The underlying mechanisms of pruritus and chronic pruritus (CP) in particular, remain poorly understood; however, current research has revealed promising new concepts in which the importance of the interaction of neuronal cells of different classes, immune cells and keratinocytes is becoming increasingly clearer. RESEARCH QUESTION: In this review article the current concepts in pruritus research are presented and summarized. MATERIAL AND METHOD: This is a review article based on the current literature. RESULTS: Different classes of sensory afferents, such as mechano-insensitive C‑fibers (histaminergic pruritus) and non-histaminergic pruriceptive C‑fibers and Aδ-fibers are involved in CP. The central sensitization in CP manifests as hyperknesis and alloknesis, the latter triggered by Aβ-fibers and Merkel cells. In recent years, the importance of inflammatory cells, such as Th1 and Th2 cells but also basophilic, eosinophilic granulocytes and mast cells has become clear. In CP there appears to be close communication between neuronal cells, immune cells and keratinocytes. Recent studies have focused on proinflammatory interleukins, such as IL-31, IL‑4 and IL-13 and their receptors. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway also plays an important role in the triggered signaling cascades that ultimately lead to pruritus perception. Therefore, in current treatment studies not only the interleukins and their receptors but also the JAK/STAT signaling pathway are directly targeted. CONCLUSION: The discovery of new mechanisms and interactions in CP highlights the complexity of this disease. Even if this and the treatment options derived from this are already very promising, a much better understanding of the mechanisms of CP is urgently needed in order to enable further options for an optimized treatment.
BACKGROUND: The underlying mechanisms of pruritus and chronic pruritus (CP) in particular, remain poorly understood; however, current research has revealed promising new concepts in which the importance of the interaction of neuronal cells of different classes, immune cells and keratinocytes is becoming increasingly clearer. RESEARCH QUESTION: In this review article the current concepts in pruritus research are presented and summarized. MATERIAL AND METHOD: This is a review article based on the current literature. RESULTS: Different classes of sensory afferents, such as mechano-insensitive C‑fibers (histaminergic pruritus) and non-histaminergic pruriceptive C‑fibers and Aδ-fibers are involved in CP. The central sensitization in CP manifests as hyperknesis and alloknesis, the latter triggered by Aβ-fibers and Merkel cells. In recent years, the importance of inflammatory cells, such as Th1 and Th2 cells but also basophilic, eosinophilic granulocytes and mast cells has become clear. In CP there appears to be close communication between neuronal cells, immune cells and keratinocytes. Recent studies have focused on proinflammatory interleukins, such as IL-31, IL‑4 and IL-13 and their receptors. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway also plays an important role in the triggered signaling cascades that ultimately lead to pruritus perception. Therefore, in current treatment studies not only the interleukins and their receptors but also the JAK/STAT signaling pathway are directly targeted. CONCLUSION: The discovery of new mechanisms and interactions in CP highlights the complexity of this disease. Even if this and the treatment options derived from this are already very promising, a much better understanding of the mechanisms of CP is urgently needed in order to enable further options for an optimized treatment.
Authors: Changxiong J Guo; Madison R Mack; Landon K Oetjen; Anna M Trier; Martha L Council; Ana B Pavel; Emma Guttman-Yassky; Brian S Kim; Qin Liu Journal: J Invest Dermatol Date: 2019-12-26 Impact factor: 8.551
Authors: Miriam M Düll; Martina Stengel; Vivien Ries; Marion Strupf; Peter W Reeh; Andreas E Kremer; Barbara Namer Journal: Pain Date: 2022-03-01 Impact factor: 6.961