痛情绪形成的ACC-DRN神经环路机制及电针干预研究

Pain affect is the emotional experience of pain, which is high in incidence among patients with chronic pain. The Anterior Cingulate Cortex (ACC)-Dorsal Raphe nulei(DRN) neural circuit regulates the negative emotion. Amygdala (Amyg) and Medial Thalamus (MT) are involved in the pain affect modulation through ACC. Electro-acupuncture (EA) can treat pain affect and influence ACC, Amyg and MT. Therefore, EA may possibly treat pain affect through ACC-DRN circuit via ACC, Amyg or MT. This project will observe the excitability of GABA/5-HTnergic neurons and activities of ACC and DRN in rats with pain affect, as well as the relationship between ACC-DRN circuit and pain affect via electrophysiology, optogenetics, DREADDs, calcium imaging and behavior tests. We will also explore the modulatory effect of MT and Amyg activities on ACC-DRN circuit. Based upon these work, we will further explore the interventions of EA on ACC-DRN circuit and MT and Amyg activities, which will help to unravel the novel mechanisms underlying EA intervention on pain affect.

痛情绪（Pain affect）是指痛的情绪和情感体验，在慢性疼痛患者中发生率高。大脑皮层前扣带回（ACC）-中缝背核（DRN）神经环路参与调节负性情绪，痛情绪过程中存在内侧丘脑（MT）、杏仁核（Amyg）参与ACC的调控环节。电针能有效干预痛情绪，对ACC、Amyg、MT等核团有一定调控效应，因此可能存在电针通过调节MT、Amyg兴奋性而调控ACC-DRN神经环路功能产生痛情绪的干预作用。本研究通过脑片电生理、光遗传、化学遗传、在体钙离子成像等技术和行为学检测，观察痛情绪大鼠ACC、DRN活性及GABA/5-HT能神经元活性的变化，探讨ACC-DRN神经环路功能与痛情绪形成的相关性；阐述痛情绪状态下，MT和Amyg活性对ACC-DRN神经环路功能的调制作用；在此基础上，探讨电针干预痛情绪中调控ACC-DRN神经环路功能及其与对MT、Amyg活性调节的相关性，揭示电针干预痛情绪的新机制。

痛情绪是指痛的情绪和情感体验，在慢性疼痛患者中发生率高，长期困扰疼痛患者，但其内在机制还不明确。电针可以有效干预痛情绪，但其干预机制仍不清楚。课题组主要获得以下几点结果：（1）明确了慢性炎性痛和慢性神经病理性痛均可以诱发负性情绪的产生，吻侧前扣带皮层（rACC）和中缝背核（DRN）是参与慢性痛诱发负性情绪的两个关键核团，而电针可以干预rACC和DRN的神经元活性以及抑制痛情绪；（2）明确了rACC与DRN核团之间存在谷氨酸（Glu）能神经投射关系，激活rACC(Glu)-DRN(5-HT)环路能有效缓解痛情绪（5-HT，五羟色胺），rACC(Glu)-DRN(GABA)环路不参与痛情绪的调控（GABA，γ-氨基丁酸）；电针可能通过激活rACC(Glu)-DRN(5-HT)神经环路产生对痛情绪的干预作用；（3）明确了杏仁核的基底外侧杏仁核（BLA）与rACC存在谷氨酸能神经投射联系，激活 BLA(Glu)-rACC环路可以有效缓解痛情绪，电针可能通过激活BLA(Glu)-rACC环路发挥抗痛情绪作用；（4）明确了rACC与丘脑（Th）存在谷氨酸能神经投射联系，抑制rACC(Glu)-Th环路可以明显改善大鼠的痛情绪，电针可能通过抑制rACC(Glu)-Th环路发挥抗痛情绪作用的。