Complete Freund’s adjuvant-induced decrement of pruriceptor-mediated suppression of itch
Complete Freund’s adjuvant-induced decrement of pruriceptor-mediated suppression of itch
复制标题
完全弗氏佐剂诱导的瘙痒感受器介导的瘙痒抑制作用减弱
DOI：
10.1093/abbs/gmab027
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发表时间：
2021
影响因子：
3.7
通讯作者：
Yu Weifeng
中科院分区：
文献类型：
--
作者：
Yin Wen;Liu Li;Zhou Yuxi;Zhang Yunchun;Kong Dexu;Xu Saihong;Tang Dan;Huang Dan;Wen Daxiang;Jiao Yingfu;Fan Yinghui;Gao Po;Yu Weifeng
周围炎症总是伴随着有害的感觉，要么是疼痛，要么是瘙痒，为病理变化的发生提供了保护性警告；然而，决定在某些炎症状态下是否会引起疼痛、瘙痒或两者兼而有之的机制仍远未明确。完全弗氏佐剂（CFA）含有热灭活并干燥的结核分枝杆菌，广泛用于诱导炎性疼痛模型，但 CFA 治疗如何影响瘙痒感以及可能的机制仍不清楚。在这项研究中，使用瘙痒行为测试和钙成像，我们发现与瞬时受体电位香草酸1（TRPV1）介导的组胺依赖性瘙痒和瞬时受体电位锚蛋白1（TRPA1）介导的组胺非依赖性瘙痒相关的行为和钙反应均被CFA治疗显着抑制。此外，为了探索可能的细胞机制，采用高通量单细胞RNA测序和实时PCR来检测CFA诱导的背根神经节（DRG）神经元中瘙痒相关基因的变化。我们的结果显示，尽管 CFA 治疗后伤害性 Trpv1~+ 和 Trpa1~+ DRG 神经元均增加，但大多数已知的瘙痒感受器，包括 Hrh1~+、Mrgpra3~+、Mrgprd~+、Htr3a~+、Htr1f~+、IL31ra~+、Osmr~+ 和 Lpar3~+ DRG 神经元显着减少，这可能解释 CFA 治疗抑制瘙痒。本研究表明，CFA治疗后瘙痒感受到影响，尽管是负面的，并且在CFA治疗后观察到不同瘙痒感受器的全面而非特异性抑制，表明在CFA诱导的炎症条件下，会同时发生疼痛增加和瘙痒减少的统一适应性变化。
Peripheral inflammation is always accompanied by a noxious sensation, either pain or itch, providing a protective warning for the occurrence of pathological changes; however, the mechanisms determining whether pain, itch, or both will be elicited under certain inflammatory statuses are still far from clear. Complete Freund’s adjuvant (CFA) contains heat killed and dried Mycobacterium tuberculosis widely used to induce inflammatory pain models, but how CFA treatment affects itch sensation and the possible mechanisms are still unclear. In this study, using itch behavior testing and calcium imaging, we showed that both the behaviors and calcium responses associated with Transient Receptor Potential Vanilloid 1 (TRPV1)-mediated histamine-dependent itch and Transient Receptor Potential Ankyrin 1 (TRPA1)-mediated histamine-independent itch were significantly suppressed by CFA treatment. Furthermore, to explore the possible cellular mechanisms, high-throughput single-cell RNA sequencing and real-time PCR were used to detect CFA-induced changes of itch-related genes in dorsal root ganglion (DRG) neurons. Our results revealed that although both nociceptive Trpv1~+ and Trpa1~+ DRG neurons were increased after CFA treatment, most known pruriceptors, including Hrh1~+, Mrgpra3~+, Mrgprd~+, Htr3a~+, Htr1f~+, IL31ra~+, Osmr~+, and Lpar3~+ DRG neurons, were significantly decreased, which may explain that CFA treatment caused itch suppression. This study indicated that itch sensation was affected after CFA treatment, although negatively, and comprehensive but not specific suppression of different pruriceptors was observed after CFA treatment, suggesting that a unified adaptive change of increased pain and decreased itch will occur simultaneously under CFA-induced inflammatory conditions.