瘙痒症通常长期反复发作，伴有负性情绪的产生，严重影响人们的工作生活。文献报道，女性对于瘙痒的感受比男性更强烈，且由于搔抓造成的皮肤损伤也更加严重，提示雌激素可能有促痒作用。另外妊娠中后期，伴随雌激素水平明显升高瘙痒症的发病率显著提高，对孕妇及胎儿均有可能造成伤害。我们的预实验观察到：雌鼠的痒觉敏感性明显高于雄鼠；阻断雌激素α型受体（ERα）能够逆转雌激素水平上升导致氯喹（CQ）诱发搔抓行为的增加；ERα在脊髓背角可能通过胃泌素释放肽受体（GRPR）发挥促痒作用。本研究拟利用CQ诱发瘙痒模型，从ERα参与调节脊髓GRPR神经元的突触可塑性机制，核受体机制和膜受体机制入手，综合运用多种转基因动物，结合电生理学、分子生物学、行为药理学等方法，从动物和细胞两个层面深入研究ERα通过GRPR神经元易化痒觉传递的分子机制，以期为临床上雌激素相关的瘙痒症，尤其是妊娠期瘙痒症的治疗提供实验依据和新的思路。

Pruritus usually recurs over a long period of time with negative emotions. This brings a lot of trouble to people's work and life. It has been proved that woman’s feelings of itching are stronger than man's, at the same time, the skin lesions are more serious. It suggesting that estrogen may have an enhancement effect. Besides that, in the middle and late pregnancy, due to the obvious increase in estrogen levels in pregnant women, which may cause the incidence of pruritus increased significantly and even cause damage to pregnant women and the unborn fetus. Our preliminary experiments observed that blocking ERα can reverse the increase in chloroquine (CQ)-induced scratching behavior due to rising of estrogen levels. And estrogen receptor alpha (ERα) promotes itch sensation transmission through GRPR neurons in superficial dorsal horn of the spinal cord. Therefore, this project would start from chloroquine induced itch model, focus on the mechanisms of ERα involved in regulating synaptic plasticity in spinal cord GRPR neurons, nuclear receptor mechanism and membrane receptor mechanism, utilizing multiple transgenic animals, electrophysiological, molecular biological, behavioral pharmacological techniques to clarify the molecular mechanisms of ERα facilitating itch transmission through GRPR neurons and to provide experimental basis and new ideas for the treatment of clinical estrogen-related pruritus, especially pruritus during pregnancy.