吗啡是一种具有强效镇痛作用的药物，用于治疗临床顽固性疼痛。吗啡类药物的长期使用易产生成瘾等多种副作用，阻碍了其广泛应用。吗啡主要通过mu型阿片受体（MOR）发挥镇痛作用。然而，目前我们对于MOR参与痛觉调控的神经环路机制认识还十分有限。在前期研究中，我们建立了条件性敲除及在特定类型神经元中重新表达MOR的遗传学小鼠模型。前期结果表明，中枢神经系统内各类神经元中表达的MOR在急性痛的调控中发挥不同的作用。本项目将在前期结果的基础上，利用多种MOR相关的遗传学小鼠品系，结合行为学分析，系统性地研究脊髓内各类神经元中表达的MOR在介导吗啡在急、慢性疼痛中的作用。我们将利用电生理学结合光遗传学技术研究脊髓背角MOR+神经元在慢性痛中的活性变化，探究其与脊髓投射神经元间的突触联系及性质。我们的研究将从细胞和神经环路水平深度解析脊髓背角神经元中的MOR受体和MOR+神经元参与痛觉信息调控的神经机制。

Morphine is a powerful drug for treating severe pain. Numerous adverse side effects associated with chronic use of opioids seriously limit the widespread use. Morphine mainly exerts analgesic effect via mu-opioid receptor (MOR). We have created several transgenic animal relate to MOR. In the previous study, we found that MOR expressed in diverse neuronal populations of central nervous system provides different function to morphine-induced acute pain modulation. But the neural circuits underlying the role of MOR in nociception modulation remain obscure. Here, we sought to explore the differential contribution of MOR expressed on specific spinal neuronal populations in nociception modulation. We will take advantage of various MOR-related genetic mouse lines, coupled with behavioral analysis, to systematically investigate the role of MOR in mediating morphine in acute and chronic pain. Subsequently, we will further determine the plasticity of MOR positive neurons in the dorsal spinal cord in chronic pain. In addition, with a combination of slice electrophysiological and optogenetic techniques, we will explore the synaptic connections between the MOR positive neurons and spinal projection neurons. Thus, our studies will reveal novel cellular and circuit mechanisms underlying the functional role of spinal MOR in the modulation of nociception.