G-Protein-Coupled Estrogen Receptor (GPER) in the Rostral Ventromedial Medulla Is Essential for Mobilizing Descending Inhibition of Itch
G-Protein-Coupled Estrogen Receptor (GPER) in the Rostral Ventromedial Medulla Is Essential for Mobilizing Descending Inhibition of Itch
复制标题
头端腹内侧髓质中的 G 蛋白偶联雌激素受体 (GPER) 对于调动瘙痒的下行抑制至关重要。
DOI：
10.1523/jneurosci.2592-20.2021
复制
发表时间：
2021-09-15
影响因子：
5.3
通讯作者：
Rong, Weifang
中科院分区：
文献类型：
--
作者：
Gao, Ting;Dong, Li;Rong, Weifang
慢性瘙痒是一种麻烦的情况，往往难以治愈。新的证据表明，中脑导水管周围灰质（PAG）-延髓头端腹内侧（RVM）通路可能在瘙痒的调节中发挥重要作用，但细胞组织和分子机制仍不完全清楚。在这里，我们报告说，一组RVM神经元独特地表达G蛋白偶联雌激素受体（GPER），介导的下降抑制瘙痒。我们发现大鼠和小鼠RVM中的GPER+神经元在慢性瘙痒条件下被激活。RVM GPER+神经元的选择性消融或化学发生抑制会导致机械性变感并增加对瘙痒剂的反应，而GPER+神经元的化学发生激活会消除瘙痒反应，这表明GPER+神经元具有止痒作用。此外，GPER缺陷小鼠和大鼠的任何性别表现出超敏反应的机械和化学瘙痒，可逆的表型的m型阿片受体（莫尔）拮抗作用。此外，在野生型慢性瘙痒模型中检测到RVM中显著的莫尔磷酸化，但在GPER-/-大鼠中未检测到。因此，GPER不仅识别了一群延髓抗癫痫神经元，而且还可能通过调节阿片信号来决定抗癫痫的下行音调。
Chronic itch is a troublesome condition and often difficult to cure. Emerging evidence suggests that the periaqueductal gray (PAG)-rostral ventromedial medulla (RVM) pathway may play an important role in the regulation of itch, but the cellular organization and molecular mechanisms remain incompletely understood. Here, we report that a group of RVM neurons distinctively express the G-protein-coupled estrogen receptor (GPER), which mediates descending inhibition of itch. We found that GPER+ neurons in the RVM were activated in chronic itch conditions in rats and mice. Selective ablation or chemogenetic suppression of RVM GPER+ neurons resulted in mechanical alloknesis and increased scratching in response to pruritogens, whereas chemogenetic activation of GPER+ neurons abrogated itch responses, indicating that GPER+ neurons are antipruritic. Moreover, GPER-deficient mice and rats of either sex exhibited hypersensitivity to mechanical and chemical itch, a phenotype reversible by the m type opioid receptor (MOR) antagonism. Additionally, significant MOR phosphorylation in the RVM was detected in chronic itch models in wild-type but not in GPER-/- rats. Therefore, GPER not only identifies a population of medullary antipruritic neurons but may also determine the descending antipruritic tone through regulating m opioid signaling.