Distinct Reactivity of Transient Receptor Potential Vanilloid Subtype 1 in a Murine Model of Atopic Dermatitis with Serious Scratching

Yan Xia, A. Tanaka, K. Oida, A. Matsuda, H. Jang, Y. Amagai, S. Ishizaka, H. Matsuda
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Abstract

Background: Abnormality in skin sensitivity may be responsible for unbearable itch in patients with atopic dermatitis (AD). Objectives: We evaluated reactivity of NC/Tnd mice, a model for human AD, against various experimental stimulations. Methods: Several behavioral tests were performed after external stimuli were applied to NC/Tnd mice. Transient receptor potential vanilloid subtype 1 (TRPV1) reactivity of neuronal cells collected from the dorsal root ganglions (DRG) was analyzed with a Ca ++ influx test. Finally, we evaluated suppressive effect of capsaicin on atopic itch of NC/Tnd mice. Results: Pain responses to heat, acidic stimulation, and capsaicin injection, which are transduced through TRPV1, were decreased in NC/Tnd mice, when compared to two standard strains BALB/c and C57BL/6 mice. The reactivity of the primary neurons isolated from DRG to capsaicin was markedly reduced in NC/Tnd mice. Topical application of histamine evoked scratching in NC/Tnd mice as well as other two strains; however, the scratching intensities induced by non- histamine pruritogens were significantly lower in NC/Tnd mice comparing to the two strains. In conventional NC/Tnd mice with AD, topical application of capsaicin reduced the scratching behavior. Conclusion: TRPV1 is associated with both pain and itch sensation; however, abnormalities in TRPV1 reactivity may in- volve in severe itch in NC/Tnd mice.
瞬时受体电位香草蛋白亚型1在严重抓挠性特应性皮炎小鼠模型中的明显反应性
背景:皮肤敏感性异常可能导致特应性皮炎(AD)患者难以忍受的瘙痒。目的:研究人类AD模型NC/Tnd小鼠对各种实验刺激的反应性。方法:对NC/Tnd小鼠施加外部刺激后,进行多项行为测试。用钙离子内流试验分析了从背根神经节(DRG)采集的神经细胞的瞬时受体电位香草样蛋白亚型1 (TRPV1)的反应性。最后,我们评价了辣椒素对NC/Tnd小鼠特应性瘙痒的抑制作用。结果:与两种标准菌株BALB/c和C57BL/6小鼠相比,NC/Tnd小鼠对TRPV1介导的热、酸刺激和辣椒素注射的疼痛反应降低。在NC/Tnd小鼠中,DRG分离的原代神经元对辣椒素的反应性明显降低。局部应用组胺引起NC/Tnd小鼠及其他两种品系的抓伤;而非组胺类瘙痒剂对NC/Tnd小鼠的抓痕强度明显低于两种毒株。在常规NC/Tnd AD小鼠中,局部应用辣椒素可减少抓挠行为。结论:TRPV1与疼痛和瘙痒感觉均相关;然而,TRPV1反应性异常可能与NC/Tnd小鼠严重瘙痒有关。
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