催产素抑制突触前可塑性参与慢性痛相关焦虑的调控机制研究

慢性痛和痛相关情绪是人类主要的健康问题之一。焦虑和抑郁是慢性痛伴发的主要负性情绪，且会加重患者的疼痛感觉。但到目前为止，我们对慢性痛及痛相关情绪的中枢调控机制仍不清楚。前扣带回皮层（ACC）的突触可塑性在疼痛感知和情绪调节中伴有非常重要的作用。人体内源性多肽催产素（Oxytocin，OXT）具有镇痛和抗焦虑作用，但OXT是否通过影响突触可塑性来参与对慢性痛和焦虑的调节不得而知。我们前期研究发现小鼠ACC微量注射OXT可以降低腓总神经结扎（CPN）引起的痛敏和焦虑行为，且OXT具有抑制ACC突触前传递长时程增强（pre-LTP）的作用。因此，我们猜测OXT可能通过抑制突触可塑性来调节慢性痛和焦虑行为。本项目拟通过行为学、膜片钳电生理、分子生化、光遗传以及双光子钙成像等技术，研究ACC突触可塑性参与OXT抗慢性痛焦虑的分子机制，以期为慢性痛和痛相关情绪的中枢调控机制提供新的研究线索和理论依据。

Chronic pain and pain-related emotions are one of the major human health problems. Chronic pain is often accompanied by negative emotions such as anxiety and depression, and these negative emotions will also increase the feeling of pain. But so far, we have not yet understood the central mechanism of chronic pain and pain-related emotions. Synaptic plasticity in the anterior cingulate cortex (ACC) plays an important role in pain perception and emotion regulation. The endogenous peptide oxytocin (OXT) in humans has analgesic and anti-anxiety effects, but whether OXT is involved in the regulation of chronic pain and anxiety by affecting synaptic plasticity is unknown. Our previous research found that microinjection of OXT in mice with ACC can reduce the hyperalgesia and anxiety behaviors caused by ligation of the common peroneal nerve (CPN), and OXT has the effect of inhibiting pre-synaptic long-term potentiation of ACC (pre-LTP). Therefore, we hypothesized that OXT might regulate chronic pain and anxiety by inhibiting synaptic plasticity. This project intends to study the molecular mechanism of ACC synaptic plasticity participating in analgesic and anti-anxiety of OXT through behavioral, patch-clamp electrophysiology, biochemical and molecules, optogenetics, and two-photon calcium imaging approaches, and to provide new research clues and theoretical basis for the central control mechanism of chronic pain and pain related emotions.