Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100005, China.
Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.
Mol Brain. 2021 Jan 19;14(1):15. doi: 10.1186/s13041-021-00730-9.
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.
慢性瘙痒是一种常见于神经疾病的症状。有人假设慢性瘙痒可能是由于瘙痒信号通路的敏化所致，但机制尚不清楚。在本研究中，我们建立了一个小鼠慢性压迫背根神经节（CCD）模型，并将各种瘙痒原和致痛原注射到受压背根神经节（DRG）同侧小腿皮肤。与未处理的小鼠相比，在注射瘙痒原（包括组胺和 BAM8-22）后，CCD 小鼠的瘙痒相关行为明显增加，但在注射辣椒素后则没有，尽管所有上述试剂均引起注射部位疼痛相关行为增强。此外，我们还研究了这种模型中瘙痒原是否会增强 DRG 神经元的活动。体内钙成像显示，受压的 DRG 神经元对组胺和 BAM8-22 的反应增强。免疫荧光染色也显示组胺受体 H1 和辣椒素受体 TRPV1 在 DRG 神经元中显著上调。我们的研究结果表明，初级瘙痒神经元的敏化可能是小鼠慢性压迫 DRG 后瘙痒感增强的基础，可能在神经疾病中的慢性瘙痒中发挥作用。
