临床上疼痛和抑郁常常伴行, 但其发病机制仍不清楚。申请人前期研究发现伏隔核(NAc)突触AMPA受体有调节慢性疼痛及相关抑郁样行为的作用。鉴于即早基因（IEG）的表达产物Homer1a有介导mGluR5信号改变AMPA受体并进一步影响神经兴奋信号传导的作用，我们发现Homer1a基因敲除小鼠慢性疼痛相关抑郁样行为加剧，而在NAc重新表达Homer1a后该抑郁样行为明显缓解，进一步研究发现慢性疼痛及相关抑郁改变NAc内Homer1a的表达，且Homer1a密切参与mGluR5信号调节。综上所述，结合申请人前期实验结果，我们推测NAc内Homer1a通过mGluR5信号介导AMPA受体进行突触重塑是调节慢性疼痛相关抑郁样行为的分子机制。在成功构建慢性疼痛及相关抑郁模型的基础上，利用行为学、分子生物学、免疫组织化学、基因敲除和神经电生理技术验证该假说，为改善疼痛及相关抑郁提供新型治疗方向。

Chronic pain and depression always coexist in patients. But mechanism of this comorbidity is still unclear. Our previous research showed that AMPA receptors of synapse in the Nucleus Accumbens (NAc) can regulate chronic pain and chronic pain related depressive behaviors. Researches have showed that the short immediate-early gene (IEG) Homer1a can induce mGluR5 and mediate AMPA receptors to change neural exciting signaling transition. Our study showed that Homer1aKO made chronic pain related depressive behaviors worse. However, this chronic pain related depressive behaviors could be alleviated by Homer1a re-expression in NAc. Moreover, we found chronic pain related depressive behaviors changed expression of Homer1a in NAc. And Homer1a in NAc participated in mGluR5 signaling. According to previous study, we assume that Homer1a via mGluR5 regulating synaptic plasticity of AMPA receptors in NAc could modulate chronic pain related depressive behaviors in mice. Base on the model of chronic pain and related depressive behavior, behavior study, the molecular biology technology and IHC can be used to conform our hypothesis. Furthermore, with technology of gene regulation and neuro electrophysiology, we are going to explore the mechanism of Homer1a and mGluR5 is key to manipulate chronic pain and related depressive behaviors in NAc. This study can provide us a novel direction for clinical pain and related depression.