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Atopic dermatitis (AD), a chronic, highly pruritic skin disorder, impairs quality of life (QoL). Janus kinase inhibitors suppress inflammatory and pruritus-associated cytokine signaling in AD.
Learn More >To evaluate the efficacy of orvepitant (10 or 30 mg given once daily, orally for 4 weeks), a neurokinin-1 receptor antagonist, compared with placebo in reducing the intensity of epidermal growth factor receptor inhibitor (EGFRI)-induced intense pruritus.
Learn More >Recurrent and intractable chronic itch is a world-wide problem but mechanisms, especially the neural mechanisms, underlying chronic itch still remain unclear. In this study, we investigated the peripheral and spinal mechanisms responsible for prolonged itch in a mouse model of allergic contact dermatitis (ACD) induced by squaric acid dibutylester (SADBE). We found that repeated exposure of mice to SADBE evoked persistent spontaneous scratching and significantly aberrant cutaneous and systemic immune responses lasting for weeks. SADBE induced itch requires both nonhistaminergic and histaminergic pathways, which are likely relayed by gastrin-releasing peptide receptor (GRPR) and natriuretic peptide receptor A (NPRA) in the spinal cord respectively. Employing genetic, pharmacology, RNAscope assay and cell-specific ablation methods, we dissected a neural circuit for the prolonged itch formed as Grpr neurons act downstream of Npr1 neurons in the spinal cord. Taken together, our data suggested that targeting GRPR and NPRA may provide effective treatments for ACD associated chronic pruritus.
Learn More >Small fiber neuropathy (SFN) is a disease of intraepidermal nerves fibers (IENF) (myelinated Aδ and unmyelinated C-fibers) prevalent in about 53/100,000 people. Mostly idiopathic, SFN can have various etiologies as alcoholism, diabetes, immune-mediated or infectious diseases. SFN commonly affects limbs in a distal to proximal gradient and manifests as various sensory symptoms. The diagnosis of SFN must fulfill following criteria : 1- a symptomatology consistent with neuropathic pains and autonomic complaints; 2- no central or motor involvement; 3- no nervous trunk achievement detected on electromyogram; 4- a reduction of IENF density (IENFD) in the distal area measured on skin biopsy ("gold standard" for diagnosis). This article is protected by copyright. All rights reserved.
Learn More >Pruritus is one of the most common dermatologic complaints and, as the most common dermatologic symptom, is a major contributor to frequent dermatology visits. Chronic pruritus mirrors another major medical condition faced by millions of Americans each year – chronic pain. In older literature, pain and pruritus were thought to have been conveyed by the same C fiber, and the proportion contributing to pruritus was just a small subset of this general fiber. Overall, pain and pruritus share many integral similarities. Although these sensations both initiate the body's awareness to injury, pain and itch may have evolved for sensing different damages such as a burrowing parasite or a noxious stimulus, respectively. This seems to have been validated through analyses of their pathophysiology, acute and chronic conditions, and treatment modalities. However, their symptoms and intrinsic mechanisms vary considerably. It is important to view pruritus in more of an overall, whole body experience, rather than just the sensory aspect. Future studies should investigate the psychological treatment of chronic pruritus, considering the immense similarities with its chronic pain counterpart.
Learn More >Itch is a defining symptom of atopic dermatitis. Crosstalk between keratinocytes, the immune system, and non-histaminergic sensory nerves is responsible for the pathophysiology of chronic itch in atopic dermatitis. An expanding understanding of the contribution of the nervous system and its interaction with immune pathways in atopic itch are helping to identify new therapeutic strategies.
Learn More >Significant unmet need exists for long-term treatment of moderate-to-severe atopic dermatitis (AD).
Learn More >Atopic dermatitis (AD) is a highly pruritic chronic inflammatory skin disorder. Ruxolitinib, a selective inhibitor of Janus kinase (JAK)-1 and JAK2, potently suppresses cytokine signaling involved in AD pathogenesis.
Learn More >Difelikefalin is a peripherally restricted and selective agonist of kappa opioid receptors that are considered to be important in modulating pruritus in conditions such as chronic kidney disease.
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