痛觉过敏是机体对伤害性刺激反应增强的神经过程，主要表现为中枢神经元的兴奋性增高和伴发的负性情绪反应等，但是神经环路机制尚不清楚。前扣带回皮层（ACC）是神经病理性疼痛发生发展及调控的重要脑区，伏隔核（NAc）与PAG和VTA有双向投射，参与中枢镇痛和疼痛相关主观感觉。课题组前期研究发现，ACC神经元兴奋性增强可影响痛阈，ACC向NAc的投射与疼痛伴发负性情绪相关。基于NAc的投射关系，本研究设想：NAc胆碱能神经元接受ACC兴奋性传入并调节投射神经元功能，影响神经病理性疼痛的痛阈以及疼痛相关情绪反应，是导致中枢痛觉过敏的关键。为此，拟采用多种转基因小鼠结合在体电生理记录、光遗传学和化学遗传学、行为学、病毒示踪、神经递质检测和脑片膜片钳等技术，研究NAc参与痛觉调制和疼痛相关情绪的神经环路，并通过调控NAc胆碱能神经元改善痛觉过敏。期望为干预或防止疼痛中枢敏化，以及相关治疗策略提供理论依据。

Hyperalgesia is a neuropathic process in which the body responds to nociceptive stimuli. It is mainly characterized by the increased excitability of neurons in central nervous system and the accompanying negative emotional reactions. However, the mechanism of neural circuit is still unclear. The anterior cingulate cortex (ACC) is one of the most important brain area for the development and regulation of neuropathic pain. The nucleus accumbens (NAc) plays an important role in regulating pain-related sensation by two-way projection with periaqueductal gray matter (PAG) and ventral tegmental area (VTA). Previous studies in this project have found that excitability of ACC neurons can affect pain threshold, and the projection of ACC to NAc is related to pain accompanied by negative emotions. Based on the projection relationship of NAc and our previous work, the research hypothesis is put forward. NAc cholinergic neurons receive ACC excitatory afferents and regulate the function of projection neurons, affecting pain threshold and pain-related emotional responses of neuropathic pain, which are the critical factors leading to central hyperalgesia. This project will adopt in vivo electrophysiological recording, photogenetics and chemical genetics, behavioral, viral tracing, neurotransmitter detection and patch clamp techniques with transgenic mice to study the neural circuits involved in pain modulation and pain-related emotions, and to improve hyperalgesia by regulating NAc cholinergic neurons. It is expected to provide theoretical basis for intervention or prevention of pain sensitization and related treatment strategies.