电针干预慢性炎性痛伴发痛情绪的杏仁核神经肽S调控机制

Pain-related emotion refers to pain with bad feeling such as anxiety, depression. It is estimated that 60%-80% of chronic pain patients are suffering from seriously pain-related emotion, is one of the major dimensions of pain. The clinical curative effect is not significant. It is very important to understand its mechanism and effective treatment. Recently discovered that neuropeptide S (NPS) could inhibit pain-related emotion through suppressing the amygdala neuron activity, which could induce the pain-related emotion. Other and our previous research preliminary suggested that electroacupuncture (EA) could intervene effectively the pain-related emotion, and the amygdala was the nuclear that involved in EA’s analgesic effect. So EA maybe promote the NPS expression to intervene the pain-related emotion through inhibiting the activity of amygdala neuron. We will establish the pain-related emotion with chronic inflammatory pain model, observe the change of sensory behavior, emotional behavior, and the amygdala neuron activity at different time, and analyze the correlation test among them. To illustrate mechanism that NPS is involved in regulating the pain-related emotion through inhibiting the amygdala neuron activity, by detecting the effect of NPS on amygdala neuron activity which is closely related to pain-related emotion. On the base, we will use EA treatment the pain-related emotion model, observing the emotional behavior, neuron activity which is closely related to pain-related emotion, positive and protein expression level of NPS in the amygdala, and the current and amplitude induced by NPS. The results of study will explore the amygdala NPS mechanism of EA regulating the pain-related emotion. Further, through pharmacology means and patch clamp technique to validate the mechanism from different angles. The research analysis the pain from the perspective of emotional pain, will contribute to more comprehensive understanding of the relation between the pain and emotion, to discuss the mechanism of pain-related emotion and new mechanism of EA on intervening pain-related emotion, and provide scientific evidence to formulate novel treatment strategy of EA on regulation pain-related emotion in clinic.

痛情绪是指疼痛伴发的焦虑、抑郁等不良情绪。60%-80%的慢性疼痛患者会伴发痛情绪，目前临床疗效不佳，了解其机制并进行有效治疗尤为重要。研究证明神经肽S（NPS）可通过抑制杏仁核神经元活性干预痛情绪。电针可有效干预痛情绪，杏仁核是其调控痛情绪的重要核团。电针有可能通过促进NPS的表达、抑制杏仁核神经元活性干预痛情绪。本项目拟通过建立慢性炎性痛伴发痛情绪大鼠模型，观察不同时间点感觉、情绪行为和杏仁核神经元活性改变及其相关性，和外源性NPS对上述指标的作用，明确NPS调控痛情绪的杏仁核神经元活性机制。在此基础上介入电针干预，观察其对痛情绪大鼠情绪行为、杏仁核神经元活性、NPS表达、NPS诱发内向电流幅值、频率的干预作用，探讨电针干预痛情绪的杏仁核NPS调控机制。进而通过药理学手段、膜片钳技术验证该机制。本研究旨在深层次探讨痛情绪的发生机制和电针干预痛情绪的新机制，为针灸治疗痛情绪提供科学依据。

痛情绪是指疼痛伴发的焦虑、抑郁等不良情绪。60%-80%的慢性疼痛患者会伴发痛情绪，目前临床疗效不佳，了解其机制并进行有效治疗尤为重要。研究证明神经肽S（NPS）可通过抑制边缘系统神经元活性干预痛情绪。电针可有效干预痛情绪，前扣带皮层、杏仁核是其调控痛情绪的重要核团。本项目拟通过建立慢性炎性痛伴发痛情绪大鼠模型，观察不同时间点感觉、情绪行为和前扣带皮层神经元活性改变及其相关性，和外源性NPS对上述指标的作用，明确NPS调控痛情绪的杏仁核神经元活性机制。在此基础上介入电针干预，观察其对痛情绪大鼠情绪行为、前扣带皮层神经元活性、NPS表达的干预作用，探讨电针干预痛情绪的杏仁核NPS调控机制。进而通过药理学手段验证该机制。结果提示，1.慢性炎性痛大鼠于造模后28d后可出现焦虑样情绪；2.造模后不同时间点前扣带皮层神经元放电频率、分布均有不同程度的变化；3.电针具有良好的镇痛、改善焦虑情绪和改变前扣带回神经元放电分布；4.痛情绪大鼠患侧ACC水平NPS和NSPR蛋白及阳性细胞表达减少；5.脑内注射NPS具有镇痛和抗焦虑作用；6.电针具有提升患侧ACC水平NPS和NPSR蛋白及阳性细胞表达，NPSR抑制剂能反转电针镇痛和抗焦虑作用；7.CFA-CPA模型大鼠双侧ACC水平NPS、NPSR阳性细胞和mRNA表达降低；电针能提升ACC和下丘脑水平的NPS和NPSR阳性细胞核mRNA表达干预CFA-CPA模型的厌恶焦虑情绪。本研究深层次探讨了痛情绪的发生机制和电针干预痛情绪的中枢NPS/NPSR机制，为针灸治疗痛情绪提供科学依据。