代谢型谷氨酸受体1和5与瞬时受体电位香草酸受体通道1在子宫颈扩张相关的内脏痛中的作用

It is well-known that the uterine cervical dilation is a major resource of the labor pain, abortion pain and femal pelvic pain. Unfortunately, the exact mechanism by which uterine cervical dilation produces, maintains and transmits visceral pain has still unclear so far, which is why there is no ideal method for labor analgesia. The upcoming study would aim, with an uterine cervical distension model of rats which has been well accepted for labor pain study, 1) to investigate that alteration of glutamate, metabotropic glutamate receptor (mGlu5 and mGlu1) expression, transient receptor potential vanilloid receptor subtype 1 (TPRV1) expression in uterine cervix, dorsal root ganglion (DRG) and spinal sections and electromyographic response in the rectus abdominis muscle after cervical distending. 2) to investigate that alteration of electromyographic response in the rectus abdominis muscle and alteration of glutamate level in uterine cervix, DRG and spinal section after cervical distending in rats administrated with antagonist of mGlu5 (MPEP), or antagonist of mGlu1 (CPCCOEt) in cervix or subarachnoid space, or in rats with TPRV1 gene knock-out, in order to explore the roles of mGlu1 and mGlu5 and TPRV1in the producing, maintaining and transmitting of uterine cerival dilatation induced visceral pain. This planned study would be expecting to show a theory for developing an ideal method for labor analgesia.

子宫颈扩张是分娩痛、人流痛以及女性内脏性盆腔痛的主要原因。子宫颈扩张性内脏痛的产生、维持、传导的确切机制尚未明确，导致至今还缺乏理想有效的分娩镇痛方法。本研究拟运用本课题组改良过的大鼠宫颈扩张模型（UCD），以宫颈扩张作为内脏痛发生源，观察大鼠（瞬时受体电位香草酸受体通道1，TRPV1+/+或TRPV1-/-）宫颈扩张后宫颈局部、背根神经节、脊髓背角等部位谷氨酸、谷氨酸受体（mGluR５和mGluR1）、TRPV1、内脏痛运动反应指标（量化腹直肌肌电信号、背角cFOS阳性神经元数量）的变化，并进一步观察宫颈局部或鞘内应用谷氨酸受体阻滞剂对内脏痛运动反应指标的影响。以探讨代谢型谷氨酸受体1和5、瞬时受体通道在宫颈扩张性内脏痛（特别是分娩痛）中的作用及其机制，为开发新型、有效、理想的此类内脏痛的镇痛（分娩镇痛）方法提供理论基础。

为了探索谷氨酸受体及瞬时受体电位香草酸受体通道1(TRPV1)在宫颈扩张过程中的作用及机制，本课题组开展了以下研究：(1建立了大鼠宫颈扩张的内脏痛模型，观察内脏痛反应指标c-fos和肌电图的变化，以及谷氨酸受体和TRPV1的表达和分布。（2）进行宫颈局部注射mGluR1和mGluR５阻滞剂后，观察谷氨酸受体和TRPV1的表达和分布，cFOS阳性神经元数量的变化，以及腹直肌肌电信号量化变化。（3）进行鞘内注射mGluR1和mGluR５阻滞剂后，观察TRPV1的表达和分布，cFOS阳性神经元数量的变化，以及腹直肌肌电信号量化变化。通过以上研究，我们取得了以下成果：（1）成功建立了大鼠宫颈扩张的内脏痛模型。（2）观察到谷氨酸受体和TPRV1的表达在模型中随宫颈扩张压力的升高而增加。（3)应用谷氨酸受体阻滞剂抑制了宫颈扩张引起的TRPV1在脊髓水平表达的增加。以上研究结果提示了谷氨酸受体和TRPV1在此模型中的疼痛传导作用及其相互作用的机制，为谷氨酸受体阻滞剂作为临床分娩镇痛提供了新的依据。