慢性痛状态下岛叶神经元兴奋性突触传递可塑性变化的机制

慢性痛严重影响人类健康和生活质量，且常导致负性情感反应，甚至自杀。大脑岛叶(IC)与慢性痛和负性情绪反应关系密切，但机制不清。我们的前期研究表明，慢性痛时IC神经元的兴奋性突触传递发生以动作电位放电长时程增强为主的可塑性变化。本项目拟以IC兴奋性神经元突触传递可塑性变化的机制为对象，综合应用神经科学的先进方法，在明确慢性痛及其引起负性情感反应的基础上，用Fos-GFP 小鼠制作慢性痛模型动物，进一步深入探讨：⑴IC内兴奋性突触数量以及谷氨酸受体（NR2B 和GluR1）密度、移位（trafficking）、相互之间的共存、磷酸化情况；⑵IC内Fos 阳性神经元、向杏仁核投射神经元的形态学和电生理学特征；⑶IC内Fos 阳性神经元、向杏仁核投射神经元的突触传递可塑性变化及其发生机理。我们期望通过研究揭示IC神经元兴奋性突触传递可塑性变化与慢性痛及负性情感反应的关系，为其防治提供依据。

Chronic pain severely affects human health and life quality, and often leads to negative emotional responses, even suicide. A few recent studies have demonstrated that the insular cortex (IC) closely relates to the chronic pain and negative emotional responses, but the underlying mechanisms are still unclear. Our previous studies have revealed that chronic pain is accompanied with exciting neurotransmission plastic changes featured by long-term potentiation (LTP) in insular cortex principle neurons. In order to clarify the relationship between the exciting neurotransmission plastic changes in the insular cortex neurons and the chronic pain and negative emotional responses, in the current proposal, we will focus our investigations onto the revealing of the mechanisms of plastic changes of the insular cortex neurons under the chronic pain status. By employing the combined modern neuroscience research techniques,with chronic pain and negative emotional response model on Fos-GFP mice, we will investigate:(1) The glutamate receptors (NR2B and GluR1) density, receptor shift (trafficking), receptor co-localization, changes on phosphorylation as well as the synapses numbers involved in chronic pain; (2) The morphological and electrophysiological characteristics of the Fos positive neurons in the insular cortex and amygdala projected neurons; (3) The mechanisms of the plastic changes of the exciting synaptic neurotransmission in the Fos-positive neurons and amygdala projected neurons in the insular cortex. We expect that the present study might reveal the relationship between the chronic pain and negative emotional responses (depression, anxiety, morbid forgetfulness, morbid forgetfulness) and the plastic changes of the excitatory synaptic transmission in the insular cortex neurons under the chronic pain status. We also believe that the results of the present proposal will provide the basis for the prevention and treatment of the chronic pain and negative emotional responses.