Chronic pruritus is a symptom that commonly observed in neurological diseases. It has been hypothesized that the chronic pruritus may result from sensitization of itch-signaling pathways but the mechanisms remain obscure. In this study, we established a mouse model of chronic compression of dorsal root ganglion (CCD) and injected various pruritogenic and algogenic agents intradermally to the calf skin ipsilateral to the compressed dorsal root ganglion (DRG). Compared to the naïve mice, a significant increase in itch-related behaviors was observed in the CCD mice after the injection of pruritogens including histamine and BAM8-22, but not after the injection of capsaicin, although all the above agents evoked enhanced pain-related behaviors toward the injected site. In addition, we investigated if pruritogen-evoked activities of DRG neurons were enhanced in this model. In vivo calcium imaging revealed that compressed DRG neurons exhibited enhanced responses to histamine and BAM8-22. Immunoflorescent staining also showed that the histamine receptor H1 and the capsaicin receptor TRPV1 were significantly upregulated in DRG neurons. Our findings indicated that the sensitization of primary pruriceptive neurons may underlie the enhanced itch sensation after chronic compression of DRG in the mice, and may play a role in chronic pruritus in neurological diseases.

中文翻译：

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瘙痒感受器在小鼠背根神经节慢性压迫模型中增强对瘙痒原敏感性的作用

慢性瘙痒是神经系统疾病中常见的一种症状。据推测，慢性瘙痒可能是由瘙痒信号通路的敏感引起的，但其机制仍不清楚。在这项研究中，我们建立了背根神经节 (CCD) 慢性压迫的小鼠模型，并将各种致痒剂和致痛剂皮内注射到与压迫背根神经节 (DRG) 同侧的小腿皮肤。与幼稚小鼠相比，在注射包括组胺和 BAM8-22 在内的 CCD 小鼠中观察到瘙痒相关行为显着增加，但在注射辣椒素后没有观察到，尽管上述所有药物都引起了增强的疼痛相关行为。对注射部位的行为。此外，我们调查了 DRG 神经元的瘙痒原诱发的活动是否在该模型中得到增强。体内钙成像显示压缩的 DRG 神经元对组胺和 BAM8-22 的反应增强。免疫荧光染色还显示组胺受体 H1 和辣椒素受体 TRPV1 在 DRG 神经元中显着上调。我们的研究结果表明，原发性瘙痒神经元的敏化可能是小鼠慢性压迫 DRG 后瘙痒感增强的基础，并且可能在神经系统疾病的慢性瘙痒中发挥作用。免疫荧光染色还显示组胺受体 H1 和辣椒素受体 TRPV1 在 DRG 神经元中显着上调。我们的研究结果表明，原发性瘙痒神经元的敏化可能是小鼠慢性压迫 DRG 后瘙痒感增强的基础，并且可能在神经系统疾病的慢性瘙痒中发挥作用。免疫荧光染色还显示组胺受体 H1 和辣椒素受体 TRPV1 在 DRG 神经元中显着上调。我们的研究结果表明，原发性瘙痒神经元的敏化可能是小鼠慢性压迫 DRG 后瘙痒感增强的基础，并且可能在神经系统疾病的慢性瘙痒中发挥作用。