外周组织、神经损伤或炎症导致慢性病理性疼痛。内源性疼痛调控系统的失衡和可塑性改变是疼痛持续慢性化的关键，但其上游调节通路及具体调控机制尚未完全明了。我们前期研究显示：利用遗传药理学技术损毁丘脑室旁核（PVT）后能够明显提高慢性痛动物的机械性缩足反射阈值；同时束路追踪技术显示存在一条PVT-杏仁中央核(CeA)-中脑导水管周围灰质(PAG)的下行通路。因此我们提出慢性痛状态下PVT内神经元被激活，并通过上述通路抑制下行抑制系统，最终易化疼痛的假设。为了进一步证实该假设，本项目拟利用不同痛模型，综合运用行为药理学、电生理学、光遗传学、遗传药理学和形态学等技术观察PVT神经元在慢性痛状态下的可塑性改变，激活或关闭PVT-CeA-PAG通路对慢性痛动物行为及神经元电活动的影响，并探究其相关的细胞分子机制。希望通过上述研究发现新的疼痛调控通路，为开发有效的疼痛治疗药物提供有针对性的干预靶点。

Peripheral tissue and nerve injury or inflammation can lead to persistant pathological pain. It’s well known that the imbalance and plasticity changes of endogenous pain control system play an important role in pain chronicity. However, the regulation pathway and potential mechanism underlied pain descending modulation are still keep unclear. Our preliminary experiments showed that the mechanical paw withdrawl threshold was significantly increased in neuropathic pain rats after paraventricular nucleus of the thalamus (PVT) was damaged using pharmacogenetic methods. Moreover, it was found the existance of PVT-central nucleus of amygdala (CeA)-periaqueductal gray (PAG) pathway using antergrade and retrograde tracer tracing methods. Together with other studies, we then hypothesized that the neurons in the PVT may be activated and involved in pain descending facilitation via PVT-CeA-PAG pathway. Based on different pain models and behavioral pharmacological, electrophysiological, optogenetic, pharmacogenetic and morphological methods, we plan to first observe the plasticity changes of PVT neurons in chronic pain animals. Then we evaluate the effects of PVT-CeA-PAG pathway on nociceptive behaviors and neuronal activities during selective activation or inactivation of neurons in this pathway and try to uncover the potential cellular and molecular mechanism. Our proposed study may be helpful for discovery of new pain regulation pathway and provide intervention targets for chronic pain therapeutic.