女性激素对子宫颈扩张性内脏痛反应的影响及其可能机制

Labor pain is a typical acute visceral pain. The exact mechanism by which how labor pain happens remains unclear, resulting no ideal methods for labor analgesia so far. Given that pain sensitivity of pregnant women decrease and that female sex hormones during pregnancy elevate, we suppose that female sex hormones could have a modulation effect on labor pain. Therefore, the present study is designed, using a model of uterine cervical distension (UCD) of rat, to investigate: 1) the effect of estrogen and/or progesterone at levels similar to pregnant status on the response to uterine cervical distension; 2) the effect of estrogen and/or progesterone at levels similar to pregnant status on the expression of TRPV1 in nerves in uterine cervix and in neurons in spinal dorsal horn; 3) the effect of administration of antagonist of TRPV1 in local cervix or in cavum subarachnoidale on the response to uterine cervical distension, expecting to reveal whether there is a modulation effect of female sex hormones on visceral pain (labor pain) induced by uterine cervical distension and the underlying mechanism. With this study, we are expecting to provide a theoretical basis to develop a new, ideal medicine or method for labor analgesia.

分娩痛是典型的急性内脏痛，至今尚无理想的分娩镇痛方法,根本原因在于其确切机制尚未明了。已有的研究表明妊娠妇女的疼痛敏感性下降，而妊娠期女性激素水平处于高水平，我们推测女性激素对分娩痛有调节作用。为此，本课题拟采用大鼠子宫颈扩张模型（UCD），以子宫颈扩张为分娩痛发生源（业已证明），观察模拟妊娠水平的雌、孕激素处理后的去卵巢大鼠对子宫颈扩张刺激的反应，雌、孕激素替代后子宫颈神经纤维和脊髓背角神经元的TRPV1的表达，以及TRPV1阻断后的子宫颈扩张刺激反应改变。以探明雌、孕激素对宫颈扩张性内脏痛（分娩痛）的调节作用及可能机制。为开发新型、高效的分娩镇痛药物和方法提供理论依据。

大量的实验性研究发现，女性的痛阈和对疼痛的耐受性总体上比男性低，并且妊娠及分娩过程的妇女的疼痛（躯体痛）阈值升高，而许多学者推测此过程的痛觉变化与体内性激素水平变化有关。为了探索女性激素对分娩相关内脏痛中的调节作用机制，本课题组开展了以下研究：1）不同模式的雌激素、孕激素单独或联合预处理对去卵巢大鼠子宫颈扩张性疼痛（分娩痛）反应产生的调节作用；2）不同模式的雌激素、孕激素单独或联合长时间预处理对去卵巢大鼠子宫颈局部神经或腰段脊髓支配子宫颈的神经细胞c-fos的表达的影响；3）不同模式的雌激素、孕激素单独或联合长时间预处理通过脊髓背角雌激素受体的表达调节疼痛感受的机制。我们取得了以下成果：1）成功建立了不同模式的雌激素长效替代模型以及雌孕激素联合替代模型；2）阐明了雌孕激素替代对去卵巢大鼠子宫颈扩张性疼痛反应产生的调节作用；3）观察到不同模式的激素替代通过影响脊髓水平的雌激素受体表达调控疼痛以及相关下游炎症因子。