Itch (Philadelphia, Pa.)最新文献

Introduction: Chronic itch has been drawing much attention due to its clinical significance and the complexity of its mechanisms. To facilitate the development of anti-itch strategies, it is necessary to investigate the key players in itch sensation under chronic itch conditions. Several members of the Mrgpr family were identified as itch receptors that detect cutaneous pruritogens in primary sensory neurons. However, the role of Mrgprs in chronic itch conditions has not been well described.

Methods: Scratching behaviors of WT and Mrgpr-clusterΔ^-/- mice were examined in dry skin model and contact dermatitis model to examine the role of Mrgpr genes in mediating chronic itch sensation. Scratching behaviors of the mice were also examined in allergic itch model. Real-time PCR were performed to examine the expression level of MrgprA3 and MrgprC11 under naïve and dry skin conditions. The MrgprA3⁺ itch-sensing fibers were labeled by tdTomato fluorescence in Mrgpra3^GFP-Cre; ROSA26^tdTomato mice, and the morphology and density of those fibers in the epidermis were analyzed under dry skin condition.

Results: We showed that deleting a cluster of Mrgpr genes in mice reduced scratching behavior severely under two chronic itch conditions, namely dry skin and contact dermatitis, and the allergic itch condition. Moreover, the gene expressions of itch receptors MrgprA3 and MrgprC11 in dorsal root ganglia (DRG) were upregulated significantly under dry skin condition. Consistently, the percentage of MrgprA3⁺ itch-sensing neurons was increased as well. We also observed hyperinnervation of MrgprA3⁺ itch-sensing fibers in the epidermis of the skin under dry skin condition.

Discussion: We demonstrate that Mrgprs play important roles in mediating chronic itch and allergic itch. These findings enrich our knowledge of itch mechanism and may lead to the development of novel therapeutic approach to combat itch.

Itch can be suppressed by scratching. At the same time, scratching evokes a pleasurable sensation. In the present study, we investigated the peripheral mechanism of scratching-induced pleasurability and its association with itch relief using compression nerve block. We found that myelinated nerve fibers (Aβ-fibers and possibly Aδ-fibers), are involved in transmission of scratching-induced pleasurability. We observed that itch relief effect was the same regardless of whether the pleasurable sensation was evoked by scratching an itch, indicating that pleasure is not a necessary component to induce itch relief. This is the first study to investigate the peripheral mechanism of scratching-induced pleasurability and itch relief.

Patient care for those affected by chronic pruritus is remarkably complex due to its high prevalence and multifactorial nature. It requires a comprehensive assessment of the patient's medical history, extensive diagnostic procedures, and long treatment duration, including management of possible accompanying disorders such as sleep disturbances and mental distress. It is important to prioritize patient's needs when developing a therapeutic treatment plan. Standardized questionnaires and scales should be used to better analyze the patient history, quality of life, symptom intensity, and course of treatment. These can be distributed via digital platforms, allowing for more effective communication between the treating agents and gathering of large volumes of data in central databases. In today's health care system, it is essential for physicians with itch-related specializations and specialized itch centers to cooperate. It is thus crucial to focus efforts on the further development of specialized treatment centers and training courses for medical practitioners. There are, however, various regulatory and economic barriers to overcome in the modern health care system before patients with chronic pruritus can be offered the best possible care. Accordingly, health care authorities should be made aware of the difficulties associated with the management of chronic pruritus and of the high individual and societal burden it represents.

Vancoymycin causes red man syndrome, an itchy erythematous eruption involving the face, neck and upper torso. Atopic dermatitis also manifests itch and erythema, and staphylococcus δ-toxin contributes to this process. The antibiotic and toxin each provoke mast cell degranulation but the mechanism had not been understood. We have determined that these compounds evoke degranulation via interaction with the same receptor, MRGPRX2, on mast cells. A receptor antagonist inhibits this process. Antagonists of this receptor may have therapeutic potential.