Trigeminal mechanisms underlie distinct orofacial pain

三叉神经机制是独特口面部疼痛的基础

• 批准号: 7049503
• 负责人: Fan Wang
• 金额: $ 36.01万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-05 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7049503
• 关键词: brain mapping; central neural pathway /tract; chronic pain; functional /structural genomics; homeobox genes; innervation; laboratory mouse; microarray technology; neuroanatomy; neurogenetics; neuronal guidance; neurophysiology; oral facial pain; pain threshold; transcription factor; trigeminal nerve

DESCRIPTION: (provided by the applicant) My lab is interested in studying the molecular mechanisms and neuronal circuitry that mediate distinct orofacial pain, using the mouse as a model system. In the craniofacial region, pain transmission is mediated by the trigeminal sensory neurons that innervate diverse tissue on the entire face. Interestingly, the perceived pain originated from different areas is different. For example, the pain of a headache is usually very different from dental pain. Furthermore, different craniofacial regions tend to be associated with or develop distinct chronic pains. We hypothesize that the three trigeminal divisions innervating different targets should express distinct molecular programs and engage in distinct neural circuits, thus enabling them to mediate different orofacial pain. In Specific Aim 1, we will identify the molecular differences among the separate divisions of trigeminal ganglion using genomic approaches. The goal is to generate comprehensive lists of molecular signatures for neurons innervating distinct head/face regions and answer the question: "How heterogeneous are nociceptive trigeminal neurons". In Specific Aim 2, we will use some of the molecular markers that we already identified to genetically map the neuronal projections from specific trigeminal populations and study the nociceptive sensory maps in normal mice and in mice with experimentally induced chronic pain. These studies should allow us to address two fundamental questions in pain research: (1) Do different trigeminal neurons form convergent projections at certain locations in the hindbrain? (2) Is abnormal axon sprouting the structural basis for chronic pain? Finally, in Specific Aim 3, we will test the functions of two of the maxillomandibular expressed transcription factors to prove, in principle, that genes specifically present in some but not all trigeminal divisions are important for either their specialized development requirements or their specific functions.

描述：（由申请人提供）我的实验室有兴趣使用小鼠作为模型系统来研究介导不同口面部疼痛的分子机制和神经元回路。在颅面部区域，疼痛传递是由支配整个面部不同组织的三叉神经感觉神经元介导的。有趣的是，来自不同部位的感知疼痛是不同的。例如，头痛的疼痛通常与牙痛有很大不同。此外，不同的颅面部区域往往与不同的慢性疼痛相关或产生不同的慢性疼痛。我们假设，支配不同目标的三个三叉神经分支应该表达不同的分子程序并参与不同的神经回路，从而使它们能够调节不同的口面部疼痛。在具体目标 1 中，我们将使用基因组方法识别三叉神经节不同分支之间的分子差异。目标是生成支配不同头/面部区域的神经元的分子特征的全面列表，并回答以下问题：“伤害性三叉神经元的异质性如何”。在具体目标 2 中，我们将使用一些已经确定的分子标记来对特定三叉神经群的神经元投射进行基因图谱，并研究正常小鼠和实验诱发慢性疼痛的小鼠的伤害性感觉图。这些研究应该使我们能够解决疼痛研究中的两个基本问题：（1）不同的三叉神经元是否在后脑的某些位置形成会聚投射？ (2)异常轴突萌发是慢性疼痛的结构基础吗？最后，在具体目标 3 中，我们将测试两个上颌表达转录因子的功能，以证明原则上，特定存在于某些但不是所有三叉神经分裂中的基因对于其特殊发育要求或特定功能很重要。