应激障碍引起体内糖皮质激素（GCs）水平改变，导致内侧前额叶皮质（mPFC）内神经元发生突触再可塑性，加重疼痛感觉，此现象称应激引起的痛觉过敏 (SIH)， 但对其机制还知之甚少。组蛋白乙酰化/去乙酰化是调节应激和疼痛的机制之一。我们观察到在SIH状态下，mPFC内组蛋白去乙酰化酶（HDAC）表达上调及细胞外信号调节激酶（ERK）大量激活，且都与糖皮质激素受体（GRs）阳性神经元共存，推测HDAC通过调节GCs-GRs-HSP90复合体-ERK信号通路参与SIH。本课题拟运用神经科学研究方法，研究大鼠mPFC内HDAC在慢性应激、疼痛、SIH不同状态下的表达变化，HDAC抑制剂对SIH痛行为、异常情绪以及GRs-HSP90复合体表达的影响，观察抑制HDAC的表达对mPFC内GRs阳性神经元突触再可塑性的影响。探讨HDAC如何调控GRs-HSP90参与SIH，为临床防治实践提供新策略。

Stress can cause the glucocorticoids (GCs) level in change, leading to the neurons of medial prefrontal cortex (mPFC) in the metaplasticity and exacerbating persistent pain disorder, which is named stress-induced hyperalgesia (SIH). However, the underlying mechanism is still unknown. Histone acetylation (HAC)/deacetylation (HDAC) is one of the mechanisms of regulation of stress and pain. Under the condition of SIH, the increased HDAC and phospho-extracellular signal-regulated kinase1/2 (pERK1/2) in the mPFC was observed. Most of HDAC and pERK1/2 are glucocorticoid receptor (GRs) positive neurons. We speculated that HDAC through adjusting the GCs-GRs-HSP90-ERK signaling pathway involved in SIH. By using neuroscience research method in this study, we observed the expression HDAC in chronic stress, chronic pain and SIH. We also observe the effects of HDAC inhibitors on pain behavior, abnormal emotion and expression of GRs-HSP90 complex and on the metaplasticity of mPFC neurons. This study discussed how HDAC regulated GRs-HSP90 complex in SIH, providing new prevention and treatment strategies for clinical practice.