Primary Afferent Transmission in the Trigeminal Dorsal Horn

三叉神经背角的初级传入传输

• 批准号: 8576394
• 负责人: Tally Marie Milnes
• 金额: $ 2.44万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-12-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8576394
• 关键词: Afferent Neurons; American; Anatomy; Automobile Driving; Axon; Behavioral; Biological Neural Networks; Biomedical Research; Brain; Brain Stem; Capsaicin; Cations; Cells; Cephalic; Chemicals; Complement; Confocal Microscopy; Cornea; Craniofacial Pain; Data; Depressed mood; Detection; Dura Mater; Electric Stimulation; Electrophysiology (science); Esthesia; Face; Face Processing; Fiber; Frequencies; Future; Glutamate Receptor; Glutamates; Goals; In Vitro; Individual; Investigation; Ion Channel; Label; Laboratories; Measurable; Measures; Mediating; Modeling; Molecular; Mono-S; Morphology; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; National Institute of Dental and Craniofacial Research; Nature; Neuronal Plasticity; Neurons; Neurosciences; Neurotransmitters; Nociception; Nociceptors; Nucleus solitarius; Organ; Orofacial Pain; Pain; Pain Research; Pathway interactions; Peripheral; Physiological; Population; Positioning Attribute; Process; Reporting; Research; Role; Sensory; Slice; Spinal; Stimulus; Structure; Structure of trigeminal nerve spinal tract nucleus; Synapses; Synaptic Transmission; System; Techniques; Testing; Thalamic structure; Therapeutic; Tissues; Tooth structure; Training; Transducers; Trigeminal Neuralgia; Trigeminal System; Trigeminal nerve structure; Up-Regulation; Vanilloid; Vertebral column; Vesicle; Visceral; Work; base; biocytin; career; dorsal horn; orofacial; pain behavior; patch clamp; receptor; reconstruction; relating to nervous system; response; skills; therapeutic target; trafficking; transmission process

DESCRIPTION (provided by applicant): Understanding of anatomical and physiological relationships within the neural networks driving craniofacial pain is a key step in developing effective therapeutic treatments. Many studies evaluating such networks focus on peripheral mechanisms of trigeminal nociception and on homologies between trigeminal and spinal nociceptive processing. The extended goal of this work is to investigate the cellular mechanisms underlying synaptic transmission between the central terminals of the trigeminal nerve (trigeminal afferents) and neurons located in the spinal trigeminal nucleus caudalis (Vc), a brainstem region implicated in nociceptive processing for the face. We hypothesize that synaptic connectivity of individual trigeminal afferents and neurons in the Vc is mediated by glutamate acting at non-NMDA and NMDA receptors and may be modulated by select ion channels, specifically the Transient Receptor Potential Vanilloid type 1 (TRPV1). We also believe that these functional connections may have distinct anatomical features. Both NMDA and non-NMDA receptors are observed in Vc, although their roles in mediating excitatory synaptic transmission in this region are ill-defined. TRPV1 is expressed on both peripheral and central termini of trigeminal neurons and upregulation of TRPV1 is closely associated with abnormal pain. Peripherally, TRPV1 has been characterized extensively as a molecular transducer of nociceptive information; however, the roles of centrally trafficked TRPV1 channels in pain processing remain unclear. Aim 1 will determine the functional connectivity of trigeminal afferents and Vc neurons with in vitro electrophysiological techniques assessing: synaptic latency variability as a measure of synaptic order, glutamate-mediated responses at NMDA and non-NMDA channels, and if TRPV1 modulates glutamatergic responses in Vc using brainstem synaptic transmission (e.g. NTS) as a model. Preliminary data demonstrate that individual trigeminal afferents can be identified using measures of synaptic latency variability, and chemical activation of central TRPV1 induces measurable responses. Aim 2, will determine the morphological features of Vc neurons related to synaptic latency variability and evaluate the anatomical connectivity between trigeminal afferents and Vc neurons with respect to TRPV1. The results will be integrated with findings from Aim 1 to provide a more specific understanding of the relationship between trigeminal afferent and Vc neuron subpopulations and the cellular mechanisms underlying synaptic transmission. These results will provide important, complementary anatomical and functional information about the neural networks that relay sensory information from the face to the brain, including the role of TRPV1 in the trigeminal pain pathway, and identify potential mechanisms for both neural plasticity and modulation of craniofacial pains.

描述（由申请人提供）：了解驱动颅面疼痛的神经网络内的解剖学和生理学关系是开发有效治疗方法的关键步骤。许多评估此类网络的研究重点关注三叉神经伤害感受的外周机制以及三叉神经和脊髓伤害感受处理之间的同源性。这项工作的扩展目标是研究三叉神经（三叉神经传入）中央末端和位于三叉神经尾核（Vc）的神经元之间突触传递的细胞机制，三叉神经尾核是一个与面部伤害性处理有关的脑干区域。我们假设 Vc 中各个三叉神经传入神经元和神经元的突触连接是由作用于非 NMDA 和 NMDA 受体的谷氨酸介导的，并且可能受到选择离子通道的调节，特别是瞬时受体电位香草酸 1 型 (TRPV1)。我们还相信这些功能连接可能具有独特的解剖学特征。在 Vc 中观察到 NMDA 和非 NMDA 受体，尽管它们在介导该区域兴奋性突触传递中的作用尚不明确。 TRPV1在三叉神经元的外周和中枢末端均表达，TRPV1的上调与异常疼痛密切相关。从外围来看，TRPV1 已被广泛描述为伤害性信息的分子传感器。然而，集中运输的 TRPV1 通道在疼痛处理中的作用仍不清楚。目标 1 将通过体外电生理技术确定三叉神经传入神经元和 Vc 神经元的功能连接，评估：作为突触顺序测量的突触潜伏期变异性、NMDA 和非 NMDA 通道的谷氨酸介导的反应，以及 TRPV1 是否调节 Vc 中的谷氨酸能反应使用脑干突触传递（例如 NTS）作为模型。初步数据表明，可以使用突触潜伏期变异性的测量来识别单个三叉神经传入神经，并且中枢 TRPV1 的化学激活会诱导可测量的反应。目标 2 将确定与突触潜伏期变异相关的 Vc 神经元的形态特征，并评估三叉神经传入神经和 Vc 神经元之间相对于 TRPV1 的解剖连接性。结果将与目标 1 的发现相结合，以更具体地了解三叉神经传入神经元和 Vc 神经元亚群之间的关系以及突触传递的细胞机制。这些结果将提供有关将感觉信息从面部传递到大脑的神经网络的重要、补充的解剖学和功能信息，包括 TRPV1 在三叉神经疼痛通路中的作用，并确定神经可塑性和颅面疼痛调节的潜在机制。