伏隔核雌激素及其受体表观遗传调控μ阿片受体介导疼痛性别差异研究

痛及痛觉调制存在性别差异，女性对疼痛的感受更敏感，由痛引发的负性情绪反应更为强烈和持久。研究表明，伏隔核和女性体内高水平的雌激素可能是介导痛的性别差异的神经环路和神经化学基础，但其具体分子机制仍不清楚。本项目拟通过双侧卵巢切除（OVX）和OVX术后雌激素替代制备体内不同雌激素水平模型，研究雌激素及其受体对痛觉的调节差异；基于μ-阿片系统在痛感觉和痛情绪调节和表观遗传机制对μ-阿片系统表达调控中的重要作用，我们进一步观察μ-阿片系统是否介导不同雌激素水平对痛觉的调制作用和不同雌激素水平是否启动不同的表观遗传调控机制实现对μ-阿片系统的表达调节，进而表现出痛行为差异。本项目的完成可从一个新的角度阐述伏隔核内雌激素系统对痛性别差异的调节机制，为研发新型镇痛药物提供有益靶标。

Gender difference in pain and pain modulation contributes to more sensitivity and stronger negative emotional response to pain in female. Many basic researches and clinical trials shown that nucleus accumbens and high estrogen level in female may be the neuronal circuit and neurochemical basis of gender difference in pain, whereas its molecular mechanism is still unclear. In this proposal, we investigate how estrogen and its receptors modulate pain behavior by different levels of estrogen produced by ovariectomized(OVX) and estrogen replacement. Moreover, based on the role of μ-opioid sytems in pain modulation and of epigenetic modification in expression ofμ-opioid sytems, we explore whether μ-opioid sytems and its epigenetic modification mediate the roles of estrogen in pain modulation. We aim to elucidate the novel neurobiological mechanisms of gender difference in pain, therefore to provide a solid theoretical basis for clinical therapy.