蓝斑至内侧前额叶神经投射通路在大鼠疼痛共情反应中的机制研究

Pain is a complex sensory and emotional experience. Chronic pain can be intractable and exert negative influences on patients’ health. Empathy is an ability to share the feelings of others, and pain empathy is a novel bio-psycho-social model that can be applied to both the research and the combined treatments for pain. It has been shown that the anterior cingulate cortex and anterior insular are the neural basis of pain empathy in humans, which brain areas also mediate the processing of the emotional response of self-experienced pain. Our previous work showed that pain empathy also existed in rats, and the medial prefrontal cortex was the neural basis of the pain empathy in rats, which is consistent with human studies. Moreover, we also found that the locus coeruleus-norepinephrine system was also involved in the pain empathy in rats. Locus coeruleus is the source of norepinephrine in the medial prefrontal cortex, whereas the regulatory effects of the locus coeruleus on the medial prefrontal cortex remained to be investigated. Based on our previous findings, the present proposal plans to investigate the roles of the noradrenergic projections from locus coeruleus to medial prefrontal cortex in the pain empathy of rats through behavioral, molecular biological, electrophysiological and optogenetic experiments. Hopefully, our study can unravel the mechanisms that underlie the modulation of the medial prefrontal cortex by locus coeruleus in pain empathy, and provide new evidence for the neurobiological mechanisms of pain empathy in rats.

疼痛是一种复杂的感觉和情绪体验，慢性疼痛严重困扰着病人的生活。共情是一种感知他人情绪状态的能力，而疼痛共情是一个新的生物-心理-社交模型，可为疼痛的研究和综合治疗提供新的思路。人类疼痛共情反应的中枢结构是前扣带回和前岛叶，与痛情绪的脑中枢结构一致。我们的前期研究发现大鼠间也存在疼痛共情反应，且脑结构中枢为内侧前额叶，与人类研究结果一致。此外，我们还发现蓝斑-去甲肾上腺素系统参与介导大鼠疼痛共情反应。蓝斑为投射性核团且是内侧前额叶中去甲肾上腺素能纤维的来源，但共情条件下蓝斑对内侧前额叶的调控机理尚不清楚。本课题拟在前期工作基础上，采用行为学、分子生物学、电生理学和光遗传学方法研究蓝斑至内侧前额叶神经通路在疼痛共情反应中的作用机制。期望通过本课题的研究揭示疼痛共情条件下蓝斑对内侧前额叶的调控机理，为完整的阐释大鼠疼痛共情反应的神经生物学机制提供新的实验证据。

共情是一种感知和分享他人情绪状态的能力，涉及到情绪和高级认知等功能。研究发现在非人灵长类和啮齿类动物中也存在着共情反应。我们之前的研究结果发现，一只大鼠给予疼痛刺激作为示教大鼠，另一只大鼠作为观测大鼠与接受疼痛刺激的示教大鼠进行社交后，观测大鼠出现机械性痛敏，而且只有当观测大鼠和示教大鼠为同笼饲养的大鼠时才会出现此现象。此外，我们还发现内侧前额叶皮质和蓝斑-去甲肾上腺素系统参与介导了大鼠间疼痛共情反应的发生。蓝斑核团向全脑发出去甲肾上腺素能神经支配，其对前额叶皮质的神经支配在工作记忆和注意方面发挥重要作用。本课题研究蓝斑至内侧前额叶神经投射通路在大鼠疼痛共情反应中的机制。大鼠双侧内侧前额叶内注射DBH-SAP逆向损毁向内侧前额叶发出神经投射纤维的蓝斑去甲肾上腺素能神经元后大鼠间疼痛共情反应引起的疼痛易化消失。大鼠双侧内侧前额叶内分别给予去甲肾上腺素能受体亚型α1和 β受体拮抗剂哌唑嗪和普萘洛尔可以消除疼痛共情反应引起的疼痛易化现象，而给予去甲肾上腺素能α2受体拮抗剂育亨宾对大鼠疼痛共情反应引起的疼痛易化无影响。大鼠双侧内侧前额叶内单独给予哌唑嗪、普萘洛尔和育亨宾对大鼠基础疼痛阈值无影响。本项目研究证明内侧前额叶内的去甲肾上腺素能纤维通过α1和 β受体亚型参与介导了大鼠疼痛共情反应的发生。