Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA; Department of Anesthesiology, Center for the Study of Itch & Sensory Disorders, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.
Department of Basic Medicine, Shaanxi University of Chinese Medicine, Xianyang, China.
J Invest Dermatol. 2021 Oct;141(10):2499-2508.e3. doi: 10.1016/j.jid.2021.03.015. Epub 2021 Apr 1.
Although sunburn can produce severe uncontrollable itching, the underlying mechanisms of UV irradiation‒induced itch are poorly understood because of a lack of experimental animal models of sunburn itch. In this study, we established a sunburn-related mouse model and found that broad-band UVB irradiation elicited scratching but not wiping behavior in mice. Using a combination of live-cell calcium ion imaging and quantitative RT-PCR on dorsal root ganglion neurons, H&E staining, immunofluorescence staining of skin preparations, and behavioral testing, in combination with genetic and pharmacological approaches, we showed that TRPV1-positive dorsal root ganglion neurons but not mast cells are involved in broad-band UVB irradiation‒induced itch. Moreover, both genetic and pharmacological inhibition of TRPV1 function significantly alleviated the broad-band UVB irradiation‒induced itch response. Collectively, our results suggest that broad-band UVB irradiation evokes itch sensation in mice by promoting TRPV1 channel function in dorsal root ganglion neurons and provide potential therapeutic targets for sunburn-related itch.
虽然晒伤会引起严重的无法控制的瘙痒,但由于缺乏晒伤瘙痒的实验动物模型,UV 辐射引起瘙痒的潜在机制仍不清楚。在这项研究中,我们建立了一个与晒伤相关的小鼠模型,发现宽谱 UVB 辐射会引起小鼠抓挠但不会引起擦拭行为。我们使用活细胞钙离子成像和定量 RT-PCR 联合背根神经节神经元、H&E 染色、皮肤准备的免疫荧光染色和行为测试,结合遗传和药理学方法,表明 TRPV1 阳性背根神经节神经元而不是肥大细胞参与了宽谱 UVB 辐射引起的瘙痒。此外,TRPV1 功能的遗传和药理学抑制均可显著减轻宽谱 UVB 辐射引起的瘙痒反应。综上所述,我们的研究结果表明,宽谱 UVB 辐射通过促进背根神经节神经元中的 TRPV1 通道功能引起小鼠瘙痒感,并为晒伤相关瘙痒提供了潜在的治疗靶点。