Articles: itch.
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Chronic pruritus (CP) is a multidimensional condition severely affecting the quality of life of those affected. Although a multitude of topical and systemic agents are recommended for CP of different origins, the condition often remains refractory to treatment. However, a deeper understanding of the pathophysiology of CP is leading to the development of novel antipruritic drugs. ⋯ Clinical trials have rendered promising data on the antipruritic efficacy and safety of novel drugs, but further studies are necessary to enhance our understanding of the different conditions associated with CP. High-quality clinical trial data is necessary for these agents to be approved for the treatment. Basic research should be intensified to identify pathways relevant for CP and to further the development of new specific antipruritic drugs.
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Itchiness triggers a strong urge to engage in scratching behavior, which could lead to severe skin or tissue damage in patients with chronic itch. This process is dynamically modulated. However, the neural mechanisms underlying itch modulation remain largely unknown. ⋯ However, the neural mechanism underlying the modulation of itch-evoked scratching in the brain remains elusive. Here, by combining fiber photometry, extracellular recording, and optogenetic manipulation, we show that the dopaminergic neurons in the ventral tegmental area play a modulatory role in itch-evoked scratching behavior. These results reveal a potential target for suppressing excessive scratching responses in patients with chronic itch.
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BDNF is a critical contributor to neuronal growth, development, learning, and memory. Although extensively studied in the brain, BDNF is also expressed by primary afferent sensory neurons in the peripheral nervous system. Unfortunately, anatomical and functional studies of primary afferent-derived BDNF have been limited by the availability of appropriate molecular tools. ⋯ In addition, because BDNF null mice are not viable and even Cre-mediated deletion of BDNF from sensory neurons could have developmental consequences, here we deleted BDNF selectively from sensory neurons, in the adult, using an advillin-Cre-ER line crossed to floxed BDNF mice. We found that BDNF deletion in the adult altered few itch or acute and chronic pain behaviors, beyond sexually dimorphic phenotypes in the tail immersion, histamine, and formalin tests. Based on the anatomical distribution of sensory neuron-derived BDNF and its limited contribution to pain and itch processing, we suggest that future studies of primary afferent-derived BDNF should examine behaviors evoked by activation of myelinated primary afferents.
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Neuropathic pruritus is a challenging condition that can be caused by injury or dysfunction in any part of the nervous system. A vast array of clinical pictures exist, including both localized and generalized pruritus, and their principal entities are described in this article. ⋯ The management of neuropathic itch is demanding and the majority of interventions are not curative. The best treatment options include anticonvulsants, topical anesthetics, and capsaicin.
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Chronic pruritus, or itch lasting greater than 6 weeks, is an increasingly common and debilitating medical problem. Recent studies have unveiled previously unrecognized neuroimmune axes whereby inflammatory cytokines act directly on the nervous system to promote itch. ⋯ This article reviews the pathophysiology of multiple chronic itch disorders, including atopic dermatitis, chronic idiopathic pruritus, chronic urticaria, and prurigo nodularis. Furthermore, new and emerging immunomodulatory therapies that will likely alter current treatment paradigms are discussed.