What causes itch in atopic dermatitis?
ABSTRACT Itch, the hallmark of atopic dermatitis, has a significant impact on quality of life for patients with this disease. Various central and peripheral mediators have been suggested to play a role in the pathophysiology of atopic eczema itch. Significant cross-talk occurs among stratum corneum, keratinocytes, immune cells, and nerve fibers, which are in close proximity to one another and induce itch. The impaired barrier function associated with the itch-scratch cycle further augments this vicious cycle. Recent advances in our understanding of itch pathophysiology shed light on peripheral and central neural sensitization of nerve fibers that contribute significantly to itch in atopic dermatitis. Recently, several new mediators have been described as associated with itch in atopic dermatitis, including serine proteases, interleukin 31, and nerve growth factor. This review covers the peripheral and central mechanisms and mediators involved in pathogenesis of itch in atopic dermatitis.
- SourceAvailable from: Xianyu Liu[Show abstract] [Hide abstract]
ABSTRACT: Central serotonin (5-hydroxytryptophan, 5-HT) modulates somatosensory transduction, but how it achieves sensory modality-specific modulation remains unclear. Here we report that enhancing serotonergic tone via administration of 5-HT potentiates itch sensation, whereas mice lacking 5-HT or serotonergic neurons in the brainstem exhibit markedly reduced scratching behavior. Through pharmacological and behavioral screening, we identified 5-HT1A as a key receptor in facilitating gastrin-releasing peptide (GRP)-dependent scratching behavior. Coactivation of 5-HT1A and GRP receptors (GRPR) greatly potentiates subthreshold, GRP-induced Ca2+ transients, and action potential firing of GRPR+ neurons. Immunostaining, biochemical, and biophysical studies suggest that 5-HT1A and GRPR may function as receptor heteromeric complexes. Furthermore, 5-HT1A blockade significantly attenuates, whereas its activation contributes to, long-lasting itch transmission. Thus, our studies demonstrate that the descending 5-HT system facilitates GRP-GRPR signaling via 5-HT1A to augment itch-specific outputs, and a disruption of crosstalk between 5-HT1A and GRPR may be a useful antipruritic strategy.Neuron 11/2014; 84(4):821-834. · 15.77 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The knowledge of the prevalence of common dermatoses will be useful for optimum use of valuable resources of the country. The aim of the study is to determine the pattern and prevalence of psoriasis, vitiligo and atopic dermatitis (AD) in India. This was a hospital-based study conducted on a single day in one medical college each in four zones of India. The point prevalence of dermatological cases was 9.25%. The point prevalence of psoriasis, vitiligo and AD were 8%, 9.98% and 6.75% respectively. Chronic plaque type psoriasis was the most common (50%) clinical pattern. The most common site of involvement of psoriasis was the palms. Stable type of vitiligo was common which accounted for 65.21%. Lower lip was involved in 75% of mucosal vitiligo. Lower limbs were the most common site of onset of vitiligo. AD was most prevalent in the first decade (40.7%). Personal history of atopy was present in (59.5%) patients. Dry skin was present in 92.5% of patients. Our data correlates with previous hospital-based prevalence studies of psoriasis, vitiligo and AD.Indian dermatology online journal. 11/2014; 5(Suppl 1):S6-8.
- [Show abstract] [Hide abstract]
ABSTRACT: Atopic dermatitis is a common skin disease affecting up to 10% of children and approximately 2% of adults. Atopic dermatitis exhibits four major symptoms, including intense itching, dry skin, redness and exudation. The "itch-scratch-itch" cycle is one of the major features in atopic dermatitis. The pathophysiology and neurobiology of pruritus is unclear. Currently there are no single and universally effective pharmacological antipruritic drugs for treatment of atopic dermatitis. Thus, controlling of itch is a very important unmet need in patients suffering from atopic dermatitis. This article will update progress during the past 10 years of research in the field of pruritus of atopic dermatitis, focusing on aspects of pruritogens (including inflammatory lipids, histamine, serotonin, proteinases, proteinase-activating receptors, neurotransmitters, neuropeptides, and opioid peptides), antipruritic therapies, and emerging new targets. Based on recent progress, researchers expect to identify exciting possibilities for improved treatments and to develop new antipruritic drugs acting through novel targets, such as histamine H4 receptor, gastrin-releasing peptide receptor, MrgprA3, thromboxane A2 receptor and the putative SPC receptor.Biomolecules and Therapeutics 07/2010; 18(3). · 0.84 Impact Factor