Itch Mechanisms and Circuits

Han, Liang; Dong, Xinzhong

doi:10.1146/annurev-biophys-051013-022826

Cited by 145 publications

(140 citation statements)

References 157 publications

(242 reference statements)

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“…C2, particularly C2-1, are MHNs (MI, IS) that express itch-related NPB [43], IL31RA [36] and proteinase-activated receptor 2 (PAR2) encoded by F2rl1 [44]. The thermal sensitivity of C2 correlates with the presence of Trpv1 and Trpv2 in the Nppb gene network and the role of NBP in thermal hyperalgesia [19,45].…”

Section: Functional Annotations Of Neuron Types and Related Gene-netwmentioning

confidence: 99%

Somatosensory neuron types identified by high-coverage single-cell RNA-sequencing and functional heterogeneity

et al. 2015

Cell Res

398

432

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Section: Functional Annotations Of Neuron Types and Related Gene-netwmentioning

confidence: 99%

Somatosensory neuron types identified by high-coverage single-cell RNA-sequencing and functional heterogeneity

et al. 2015

Cell Res

398

432

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“…The above phenomenon is likely due to the sensitization of itchsignaling pathways under chronic itch conditions. Sensitization of itch-signaling pathways has been proposed as a critical mechanism underlying chronic itch (41,42). In ACD and atopic dermatitis, nerve fiber densities are increased in the epidermis (43,44).…”

Section: Discussionmentioning

confidence: 99%

IL-33/ST2 signaling excites sensory neurons and mediates itch response in a mouse model of poison ivy contact allergy

Liu

Tai

Achanta

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

213

195

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Poison ivy-induced allergic contact dermatitis (ACD) is the most common environmental allergic condition in the United States. Case numbers of poison ivy ACD are increasing due to growing biomass and geographical expansion of poison ivy and increasing content of the allergen, urushiol, likely attributable to rising atmospheric CO 2 . Severe and treatment-resistant itch is the major complaint of affected patients. However, because of limited clinical data and poorly characterized models, the pruritic mechanisms in poison ivy ACD remain unknown. Here, we aim to identify the mechanisms of itch in a mouse model of poison ivy ACD by transcriptomics, neuronal imaging, and behavioral analysis. Using transcriptome microarray analysis, we identified IL-33 as a key cytokine up-regulated in the inflamed skin of urushiol-challenged mice. We further found that the IL-33 receptor, ST2, is expressed in small to medium-sized dorsal root ganglion (DRG) neurons, including neurons that innervate the skin. IL-33 induces Ca 2+ influx into a subset of DRG neurons through neuronal ST2. Neutralizing antibodies against IL-33 or ST2 reduced scratching behavior and skin inflammation in urushiol-challenged mice. Injection of IL-33 into urushiol-challenged skin rapidly exacerbated itch-related scratching via ST2, in a histamine-independent manner. Targeted silencing of neuronal ST2 expression by intrathecal ST2 siRNA delivery significantly attenuated pruritic responses caused by urushiol-induced ACD. These results indicate that IL-33/ST2 signaling is functionally present in primary sensory neurons and contributes to pruritus in poison ivy ACD. Blocking IL-33/ST2 signaling may represent a therapeutic approach to ameliorate itch and skin inflammation related to poison ivy ACD.A llergic contact dermatitis (ACD) is a common allergic skin condition caused by environmental or occupational allergens (1). In the United States, the most common cause of ACD is contact with poison ivy, which affects >10 million Americans per year (2, 3). Poison ivy ACD is also a serious occupational hazard, particularly among firefighters, forestry workers, and farmers, accounting for 10% of total U.S. Forest Services losttime injuries, and it often torments outdoor enthusiasts as well (3, 4). The major allergen in poison ivy is urushiol, contained in the oleoresinous sap of the plant and of related plants (e.g., poison oak and poison sumac) (5). An estimated 50-75% of Americans are sensitized to urushiol (6). Elevated atmospheric carbon dioxide and warming temperatures have increased the biomass of poison ivy and related plants, widened their geographic distribution, and increased plant urushiol content (7). These factors will likely increase allergenicity and result in even larger case numbers of poison ivy ACD in the future (8).The clinical manifestations of poison ivy-induced ACD are intense and persistent itch (pruritus), burning sensation, skin rashes, and swelling, followed by the appearance of vesicles in severe cases (2, 3, 9). Skin inflammation and pruritus ...

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“…In recent years, pruritus has been gained more increased interest in medicine due to its higher prevalence than thought, serious impact on quality of life such as impaired sleep quality, more depressive symptoms and higher levels of anxiety (Zachariae et al 2012) and limited efficacy of current antipruritic agents (Carstens and Akiyama 2014). The tremendous advances have been made to understand the molecular and cellular mechanisms in the transmission of itch sensation from periphery to central nervous system (Han and Dong 2014). Animal models of itch served as the major tool in these advances, from identification of novel targets and mechanisms of new therapeutics (Shimada andLaMotte 2008, LaMotte et al 2011).…”

Section: Introductionmentioning

confidence: 99%

The false-positive responses of analgesic drugs to the intradermal serotonin- and compound 48/80-induced scratches as an animal model of itch

İlkaya¹,

Yeşilyurt²,

Seyrek³

et al. 2016

Acta Neurobiologiae Experimentalis

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Intradermal injection of pruritogens such as serotonin, histamine and compound 48/80 into the skin and then, the evaluation of the scratching behavior is the commonly used animal model to advance pruritic research and drug development. However, predictive validity of this model is poorly documented. There is a close interaction between itch and pain sensations with regard to mediation through an anatomically and functionally identical neuronal pathway. One approach is whether the existing animal model of itch differentiates itch or pain to show efficacy of clinically effective analgesic drugs as a back translation. In this study, we explored the effects of different group of analgesic drugs on serotonin and compound 48/80-induced scratching behavior in Balb-C mice. Serotonin (25 μg) and compound 48/80 (100 μg) was injected intradermally in a volume of 50 μl into the rostral part of skin on the back of male mice and scratches were counted for a 30-min observation period. Morphine (1, 3, 10 mg/kg), tramadol (20, 40, 80 mg/kg), cannabinoid agonist CP 55,940 (0.1, 0.3, 1 mg/kg), paracetamol (100, 200, 300 mg/kg) and diclofenac (50, 100, 200 mg/kg) were given intraperitoneally 30 min prior to pruritogen injection. The analgesic drugs dose dependently blocked serotonin and compound 48/80-induced straching behavior with exerting complete inhibition at certain doses. Our data suggests that intradermal pruritogen-induced scratching models may not discriminate pain and itch sensations and give false positive results when standard analgesic drugs are used.

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Itch Mechanisms and Circuits

Cited by 145 publications

References 157 publications

Somatosensory neuron types identified by high-coverage single-cell RNA-sequencing and functional heterogeneity

Somatosensory neuron types identified by high-coverage single-cell RNA-sequencing and functional heterogeneity

IL-33/ST2 signaling excites sensory neurons and mediates itch response in a mouse model of poison ivy contact allergy

The false-positive responses of analgesic drugs to the intradermal serotonin- and compound 48/80-induced scratches as an animal model of itch

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