催产素易化或诱发瘙痒的外周和脊髓机制

Oxytocin (OXT) is peptide hormone mainly synthesized in the hypothalamic supraoptic and paraventricular nuclei, and gradually increasing its secretion during pregnancy. OXT can promote uterine contraction, and conducive to childbirth, and may also be involved in the control of cognitive, social behavior, addiction and pain. Pruritus is one of the most common chief complaint of pregnancy women, and the cause of many prurius which lasted until the termination of pregnancy unknown. Then, whether OXT can facilitate or induce pruritus, and whether the secretion increase is associated with pregnancy itch? Preliminary experimental results showed that: The itch susceptibility increased in nearly half of the late pregnant mice; Exogenous applying OXT can induce or facilacate scratch behavior in mice; Endogenous activating OXTergic neurons in hypothalamic paraventricular nucleus can’t directly induce pruritus, but can facilitate the scratching reaction induced by itch causing agent. Thus, we confirmed that OXT can directly induce or facilitate itch. Therefore, this project intends to do the following researches using morphological, behavioral science, electrophysiology, optogenetics techniques: The relationship between increased OXT during pregnancy (or man-made) and itch; The peripheral mechanisms of OXT facilitating or inducing pruritus; The spinal mechanisms of OXT facilitating or inducing pruritus. The purpose of the present project is to clarify the relationship between pregnancy itching and OXT, and reveal the mechanisms of OXT facilitating or inducing itch, and provide the basis for reasonable application of OXT and the prevention and cure of pregnancy itch.

催产素（OXT）是主要合成于下丘脑视上核和室旁核的激素，在妊娠期分泌逐渐增加，可促进子宫收缩，利于分娩。OXT也可参与认知、社会行为、成瘾、疼痛等的调控。瘙痒是妊娠期女性常见的主诉，大多原因不明，且一直持续到妊娠终止。那么，OXT是否可以易化或诱发瘙痒，其分泌增加与妊娠瘙痒是否有关联？预实验结果显示：近半数晚期孕鼠的痒觉敏感性增高；外源性给予OXT可诱发或易化瘙痒；内源性激活下丘脑室旁核OXT神经元不直接诱发瘙痒，但可易化致痒剂诱发的搔抓反应。由此，我们初步证实OXT可以诱发或易化瘙痒。因此，本项目拟运用形态学、行为学、电生理学、光遗传学、分子生物学等技术研究：妊娠期（或人为导致）体内OXT增高与瘙痒的关系；OXT易化或诱发瘙痒的外周机制；OXT易化或诱发瘙痒的脊髓机制。以期阐明妊娠瘙痒与OXT增多的关系，揭示OXT易化或诱发瘙痒的机制，为妊娠瘙痒的防治和OXT的合理应用提供依据。

瘙痒是妊娠期女性常见的主诉，大多原因不明，且一直持续到妊娠终止。那么，催产素（OXT）是否可以易化或诱发瘙痒，其分泌增加与妊娠瘙痒是否有关联？雌激素是否也参与妊娠瘙痒？这些一直是困扰皮肤科和妇产科医生的难题，给妊娠期瘙痒的治疗带来困难。本研究综合应用形态学、行为学、电生理学、光遗传学、分子生物学等技术手段研究了：妊娠期（或人为导致）体内OXT增高与瘙痒的关系；OXT易化或诱发瘙痒的外周机制；OXT易化或诱发瘙痒的脊髓机制。以期阐明妊娠瘙痒与OXT增多的关系，揭示OXT易化或诱发瘙痒的机制。结果显示：（1）妊娠期瘙痒确实与体内OXT含量的增多密切相关，动物实验显示无论内源性还是外源性的OXT增加，均可增加机体对痒觉的敏感性，甚至直接诱发瘙痒；（2）脊髓背角浅层，OXTR阳性神经元与GRPR及SPR存在共表达，提示OXTR可能通过GRPR或SPR阳性神经元发挥致痒效应，并将痒觉信息向中枢传递；（3）下丘脑室旁核（PVN）内OXT能神经元的激活能够易化痒觉信息的传递，并且这种易化作用是通过外周DRG中OXTR和AVPR1a所介导，而不通过PVN-脊髓背角通路所介导；（4）在外周，OXT的部分促痒效应可能是通过OXTR与TRPV1的协同效应发挥的，高浓度的OXT可使正常小鼠皮肤肥大细胞脱颗粒从而导致瘙痒；（5）体内雌激素含量的不同可能是痒觉感受性别差异的关键因素，但妊娠期雌激素含量的增加并非妊娠期瘙痒的主要原因；在外周，雌激素的促痒效应可能是通过ER-α介导的。上述研究结果初步阐明了OXT易化或诱发瘙痒的外周和脊髓机制，为妊娠瘙痒的防治和OXT的合理应用提供了依据。