Emotion, Pain and Pain Control Circuits

描述(由申请人提供)： 中脑导水管周围灰质(FAG)和毗邻的中缝背核(DRN)是 能够控制痛觉的中脑细胞群。一种共识 已经出现了PAG在启动和实施行为 应对压力、恐惧或痛苦的策略。DRN是一种 前脑5-羟色胺的主要来源，它调节许多行为并具有 与抑郁症的病理生理学有关。通过这些来控制疼痛 两个原子核很可能是多峰反应模式的单个元素 压力很大的情况。P物质(SP)是一种以玩耍著称的神经肽 在疼痛传递中起作用。释放时，SP与神经激肽1(NK1)结合 受体和沉淀受体的激活和内化。NK1 感受器在背侧和腹外侧基底核以及 DRN.在该区域，SF的局部应用具有抗伤害性，引起 局部释放内源性阿片类药物。此外，SP神经传递是 与焦虑、心血管调节和美容行为有关。 因此，PAG和DRN代表了SP可能影响的潜在部位 行为应对策略的几个个体组成部分。建议数 实验将检查NK1受体的内化，该受体由 用免疫组织化学方法观察外源性和内源性SP 探讨SP神经递质在FAG和DRN中的作用。NK1的地形 这些刺激的内化将揭示神经潜在的重叠 用来处理这些刺激的回路。此外，拟议的目标将 广泛地建立SP参与调节这些区域的神经回路。 也就是说，含有脑啡肽或5-羟色胺的神经元 NK1受体将使用光学和电子显微镜分析进行测试。 这些研究的结果将深入了解不同的模式是如何 应激刺激影响神经回路中的SP神经传递 协调防御应对策略。

DESCRIPTION (provided by applicant): The periaqueductal gray (FAG) and the adjoining dorsal raphe nucleus (DRN) are mesencephalic cell groups that can act to control pain perception. A consensus has arisen that the PAG functions in initiating and implementing behavioral coping strategies to situations involving stress, fear or pain. The DRN is a major source of forebrain serotonin, which modulates many behaviors and has been implicated in the pathophysiology of depression. Control of pain by these two nuclei is likely a single element of a multimodal response pattern to stressful situations. Substance P (SP) is a neuropeptide well known for playing a role in pain transmission. When released, SP binds the neurokinin 1 (NK1) receptor and precipitates receptor activation and internalization. The NK1 receptor is enriched within the dorsal and ventrolateral FAG as well as the DRN. In this region, focal application of SF is antinociceptive, eliciting the local release of endogenous opioids. In addition, SP neurotransmission is associated with anxiety, cardiovascular adjustments and grooming behavior. Therefore the PAG and DRN represent potential sites where SP may influence several individual components of behavioral coping strategies. The proposed experiments will examine internalization of the NK1 receptor produced by exogenous and endogenous SP using immunohistochemical methods to gain insight into the role of SP neurotransmission in the FAG and DRN. The topography of NK1 internalization by these stimuli will reveal the potential overlap of neural circuits used in coping with these stimuli. In addition, the proposed AIMS will broadly establish the neural circuitry that SP engages to modulate these areas. That is, the hypothesis that enkephalin- or serotonin-containing neurons have the NK1 receptor will be tested using light and electron microscopic analysis. The results of these studies will-yield insight into how distinct modes of stressful stimuli impact SP neurotransmission within neural circuits that coordinate defensive coping strategies.