To identify itch-related mediators and receptors that are differentially expressed in pruritic skin, we used RNA sequencing to analyze the complete transcriptome in skin from paired itchy, lesional and nonitchy, nonlesional skin biopsies from 25 patients with atopic dermatitis and 25 patients with psoriasis and site-matched biopsies from 30 healthy controls. This analysis identified 18,000 differentially expressed genes common between itchy atopic and psoriatic skin compared with healthy skin. Of those, almost 2,000 genes were differentially expressed between itchy and nonitchy skin in atopic and psoriatic subjects. Overexpression of several genes, such as phospholipase A2 IVD, substance P, voltage-gated sodium channel 1.7, and transient receptor potential (TRP) vanilloid 1, in itchy skin was positively correlated with itch intensity ratings in both atopic dermatitis and psoriasis. Cytokines such as IL-17A, IL-23A, and IL-31 had elevated gene transcript levels in both itchy atopic and psoriatic skin. However, expression of genes for TRP vanilloid 2, TRP ankyrin 1, protease-activated receptor 2, protease-activated receptor 4, and IL-10 was found to be increased only in pruritic atopic skin, whereas expression of genes for TRP melastatin 8, TRP vanilloid 3, phospholipase C, and IL-36α/γ was elevated only in pruritic psoriatic skin. This "itchscriptome" analysis will lead to an increased understanding of the molecular mechanisms of chronic pruritus and provide targets for itch treatment irrespective of disease state.

No abstract

Previous brain imaging studies investigating the brain processing of scratching used an exogenous intervention mimicking scratching, performed not by the subjects themselves, but delivered by an investigator. In real life, scratching is a conscious, voluntary, controlled motor response to itching, which is directed to the perceived site of distress. In this study we aimed to visualize in real-time by brain imaging the core mechanisms of the itch-scratch cycle when scratching was performed by subjects themselves. Secondly, we aimed to assess the correlations between brain patterns of activation and psychophysical ratings of itch relief or pleasurability of scratching. We also compared the patterns of brain activity evoked by self-scratching vs. passive scratching. We used a robust tridimensional Arterial Spin Labeling fMRI technique that is less sensitive to motion artifacts: 3D gradient echo and spin echo (GRASE) - Propeller. Active scratching was accompanied by a higher pleasurability and induced a more pronounced deactivation of the anterior cingulate cortex and insula, in comparison with passive scratching. A significant involvement of the reward system including the ventral tegmentum of the midbrain, coupled with a mechanism deactivating the periaqueductal gray matter (PAG), suggests that itch modulation operates in reverse to the mechanism known to suppress pain. Our findings not only confirm a role for the central networks processing reward in the pleasurable aspects of scratching, but also suggest they play a role in mediating itch relief.

Approximately 88% of cutaneous T-cell lymphoma (CTCL) patients are affected by pruritus that responds poorly to current antipruritic therapies. Interleukin (IL)-31, a Th2 cytokine, has been found to be increased in the serum of CTCL patients and to correlate with itch severity. This study investigated the role of IL-31 and its receptors (IL-31 receptor-alpha [IL-31RA] and OSMRβ) in the skin of CTCL patients with mild versus moderate/severe pruritus. Expression levels of IL-31, IL-31RA, and OSMRβ in the skin were measured using immunohistochemistry and correlated to pruritus severity and disease stage. In CTCL patients with moderate/severe pruritus, IL-31 was significantly elevated in the epidermis and dermal infiltrate, while IL-31RA and OSMRβ were significantly elevated only in the epidermis. Furthermore, epidermal IL-31 levels correlated to itch severity. These results show that IL-31 may play a role in CTCL pruritus by exerting indirect effects on sensory nerves through epidermal neoplastic T cells and keratinocytes to transmit itch.

No abstract