Enhanced itch elicited by capsaicin in a chronic itch model

Yu, Guang; Yang, Niuniu; Li, Fengxian; Chen, Meijuan; Guo, Changxiong; Wang, Changming; Hu, Danyou; Yang, Yan; Zhu, Changliang; Wang, Zhongli; Shi, Hao; Gegen, Tana; Tang, Ming; He, Qiang; Liu, Qin; Tang, Zongxiang

doi:10.1177/1744806916645349

Cited by 16 publications

(15 citation statements)

References 20 publications

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“…TRPV1 could be activated by various endogenous and exogenous stimuli, including capsaicin, temperature, pH, TNF-α, and pro-inflammatory cytokines and amplified the effects of inflammation [39,58]. Recent studies show that dry skin stimuli increased the expression of TRPV1 in DRG and TG neurons [59,60]. Combined with our above results, we speculate that NLRP1 inflammasome could contribute to the upregulation of TRPV1 in dry skin induced chronic itch model.…”

Section: Discussionsupporting

confidence: 78%

Spinal cord NLRP1 inflammasome contributes to dry skin induced chronic itch in mice

Fan

Gao

Song

et al. 2020

J Neuroinflammation

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Background: Dry skin itch is one of the most common skin diseases and elderly people are believed to be particularly prone to it. The inflammasome has been suggested to play an important role in chronic inflammatory disorders including inflammatory skin diseases such as psoriasis. However, little is known about the role of NLRP1 inflammasome in dry skin-induced chronic itch. Methods: Dry skin-induced chronic itch model was established by acetone-ether-water (AEW) treatment. Spontaneous scratching behavior was recorded by video monitoring. The expression of nucleotide oligomerization domain (NOD)-like receptor protein 1 (NLRP1) inflammasome complexes, transient receptor potential vanilloid type 1 (TRPV1), and the level of inflammatory cytokines were determined by western blot, quantitative real-time PCR, and enzyme-linked immunosorbent assay (ELISA) kits. Nlrp1a knockdown was performed by an adeno-associated virus (AAV) vector containing Nlrp1a-shRNA-eGFP infusion. H.E. staining was used to evaluate skin lesion. Results: AEW treatment triggers spontaneous scratching and significantly increases the expression of NLRP1, ASC, and caspase-1 and the levels of IL-1β, IL-18, IL-6, and TNF-α in the spinal cord and the skin of mice. Spinal cord Nlrp1a knockdown prevents AEW-induced NLRP1 inflammasome assembly, TRPV1 channel activation, and spontaneous scratching behavior. Capsazepine, a specific antagonist of TRPV1, can also inhibit AEW-induced inflammatory response and scratching behavior. Furthermore, elderly mice and female mice exhibited more significant AEW-induced scratching behavior than young mice and male mice, respectively. Interestingly, AEW-induced increases in the expression of NLRP1 inflammasome complex and the levels of inflammatory cytokines were more remarkable in elderly mice and female mice than in young mice and male mice, respectively. Conclusions: Spinal cord NLRP1 inflammasome-mediated inflammatory response contributes to dry skin-induced chronic itch by TRPV1 channel, and it is also involved in age and sex differences of chronic itch. Inhibition of NLRP1 inflammasome may offer a new therapy for dry skin itch.

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Section: Discussionsupporting

confidence: 78%

Spinal cord NLRP1 inflammasome contributes to dry skin induced chronic itch in mice

Fan

Gao

Song

et al. 2020

J Neuroinflammation

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“…Additionally, due to evidence that the itch in AD is histamine-independent [16], topical antihistamines would have limited to no efficacy in treating AD-related pruritus. Topical capsaicin, or chili pepper extract, has been reported to be an efficacious treatment for itch [47], yet a recent study found that topical capsaicin can actually enhance chronic pruritus, possibly due to the upregulation of Transient Receptor Vanilloid 1-expressing sensory neurons seen in chronic pruritus conditions [48]. Topical anesthetics such as lidocaine and prilocaine are known to have topical anti-pruritic effects by stabilizing sensory fibers and blocking the itch sensation.…”

Section: Topical Options For the Management Of Chronic Pruritusmentioning

confidence: 99%

Breaking the Itch–Scratch Cycle: Topical Options for the Management of Chronic Cutaneous Itch in Atopic Dermatitis

Harrison¹,

Spada²

2019

Medicines

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Chronic itch is an unpleasant sensation that triggers a desire to scratch that lasts for six weeks or more. It is a major diagnostic symptom of myriad diseases, including atopic dermatitis for which it is the most prominent feature. Chronic itch can be hugely debilitating for the sufferer, damaging in terms of both the monetary cost of treatment and its socioeconomic effects, and few treatment options exist that can adequately control it. Corticosteroids remain the first line treatment strategy for atopic dermatitis, but due to the risks associated with long-term use of corticosteroids, and the drawbacks of other topical options such as topical calcineurin inhibitors and capsaicin, topical options for itch management that are efficacious and can be used indefinitely are needed. In this review, we detail the pathophysiology of chronic pruritus, its key features, and the disease most commonly associated with it. We also assess the role of the skin and its components in maintaining a healthy barrier function, thus reducing dryness and the itch sensation. Lastly, we briefly detail examples of topical options for the management of chronic pruritus that can be used indefinitely, overcoming the risk associated with long-term use of corticosteroids.

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“…The bouts of scratching with the hind paw, directed towards the treated site, were counted. A bout of scratching is defined as a continuous scratching movement with a hind paw directed at the treated site until the hind paw is back on the floor or in the mouth 17 …”

Section: Methodsmentioning

confidence: 99%

mMrgprA3/mMrgprC11/hMrgprX1: Potential therapeutic targets for allergic contact dermatitis–induced pruritus in mice and humans

Wang

et al. 2022

Contact Dermatitis

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Background Although the Mas‐related G‐protein–coupled receptors (Mrgprs) play essential roles in itch detection, their contribution to allergic contact dermatitis (ACD)–associated itch remains unclear. Objectives To investigate whether Mrgprs are involved in ACD and whether Mrgprs can be identified as potential therapeutic targets. Methods Mrgpr‐clusterΔ–/– mice and human MrgprX1 (hMrgprX1) transgenic mice were used to evaluate the function of Mrgprs in oxazolone‐induced ACD. Results Utilizing an ACD model, we found that Mrgpr‐clusterΔ–/– mice display significantly reduced pruritus. Among 12 Mrgprs deleted in Mrgpr‐clusterΔ–/– mice, the expression of MrgprC11 and MrgprA3 was significantly increased in the ACD model, which also innervated the skin and spinal cord at higher‐than‐normal densities. The proportions of dorsal root ganglia neurons responding to bovine adrenal medulla peptide 8‐22 and chloroquine were also remarkably increased in the ACD model, resulting in enhanced itch behaviour. To study the function of human Mrgprs in ACD‐induced itch, we used hMrgprX1 transgenic mice, which rescued the severe itch defect of Mrgpr‐clusterΔ–/– mice in the ACD model. Remarkably, pharmacological blockade of hMrgprX1 significantly attenuates ACD itch in hMrgprX1 transgenic mouse. Conclusions Our study provides the first evidence that Mrgprs are involved in ACD‐induced chronic itch, which provides new avenues for itch management in ACD.

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Enhanced itch elicited by capsaicin in a chronic itch model

Cited by 16 publications

References 20 publications

Spinal cord NLRP1 inflammasome contributes to dry skin induced chronic itch in mice

Spinal cord NLRP1 inflammasome contributes to dry skin induced chronic itch in mice

Breaking the Itch–Scratch Cycle: Topical Options for the Management of Chronic Cutaneous Itch in Atopic Dermatitis

mMrgprA3/mMrgprC11/hMrgprX1: Potential therapeutic targets for allergic contact dermatitis–induced pruritus in mice and humans

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