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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瘙痒感受器在增强小鼠背根神经节慢性压迫模型中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症状。据推测，慢性瘙痒可能是由瘙痒信号通路致敏引起的，但其机制仍不清楚。在本研究中，我们建立了背根神经节（CCD）慢性受压的小鼠模型，并向受压背根神经节（DRG）同侧的小腿皮肤皮内注射各种致痒和致痛剂。与初始小鼠相比，在注射包括组胺和 BAM8-22 在内的瘙痒剂后，在 CCD 小鼠中观察到与瘙痒相关的行为显着增加，但在注射辣椒素后则没有，尽管所有上述药物都会引起与疼痛相关的增强。对注射部位的行为。此外，我们还研究了该模型中是否增强了 DRG 神经元的瘙痒原诱发活动。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，DRG 神经元中组胺受体 H1 和辣椒素受体 TRPV1 显着上调。我们的研究结果表明，初级瘙痒神经元的敏化可能是小鼠背根神经节长期受压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。