Primary and Secondary Nociceptors in Persistent Pain

持续性疼痛中的初级和次级伤害感受器

• 批准号: 7394912
• 负责人: H Richard Koerber
• 金额: $ 31.74万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-17 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7394912
• 关键词: Address; Afferent Neurons; Attenuated; Behavioral; C Fiber; Capsaicin; Cells; Chemicals; Cutaneous; Data; Development; Exhibits; Fiber; Freund' s Adjuvant; G-Protein-Coupled Receptors; Genes; Goals; Green Fluorescent Proteins; Heating; Hyperalgesia; Hypersensitivity; Inflammation; Inflammatory; Injection of therapeutic agent; Injury; Knock-in Mouse; Knock-out; Knockout Mice; Laboratories; Ligation; Maintenance; Mechanics; Mediating; Modality; Modeling; Mus; Nerve; Neurons; Neuropathy; Nociception; Nociceptors; Numbers; Output; Pain; Peptides; Persistent pain; Phenotype; Physiological; Play; Population; Posterior Horn Cells; Preparation; Process; Property; Rattus; Research Personnel; Role; Sensory; Skin; Spinal; Spinal Cord; Spinal nerve structure; Stimulus; Techniques; Testing; Thermal Hyperalgesias; Time; Transgenic Mice; Vanilloid; behavior test; dorsal horn; genetic manipulation; inflammatory neuropathic pain; inflammatory pain; mouse model; neural circuit; neurochemistry; painful neuropathy; receptor; relating to nervous system; response

The goal of the proposed studies is to examine the time course of changes in identified cutaneous sensory neurons and spinal cord neurons responsible for the development and maintenance of inflammatory and neuropathic pain states. These neurons play critical roles in processing of pain information. These studies will address three specific aims. In the first aim we will employ combined physiological and anatomical techniques to determine the properties of primary afferents and superficial dorsal horn cells in normal mice. In the second aim we will determine the properties of the same cells after inflammatory and neuropathic injury. Behavioral tests of mechanical and heat sensitivity will be compared with any changes seen in the identified neurons. In the third aim, we will use two trangenic mouse lines (one that has the capsaicin/heat channel TRPV1 knocked out, one that has the Mas-gene related G-protein coupled receptor D (Mrgdprd) knocked out and green fluorescent protein knocked in). TRPV1 has been shown to mediate some aspects of heat sensitivity, and Mrgprd is found exclusively in a population of cutaneous sensory nociceptors. We have recently found that these cutaneous nociceptors in Mrgprd-knock-out mice, have attenuated heat responses. We will determine the properties of primary afferent and secondary nociceptors in these two mouse lines following inflammatory and neuropathic injury. By comparing behavioral and neural data, we will be able to assess the effect of these genetic manipulations on the induction and maintenance of pain states following two types of injury. The data gathered in all three specific aims will be used to develop a model of neural circuits that are essential during these pain states. By comparing the three groups, we hope to elucidate the specific populations of primary afferent and secondary nociceptive neurons crucial to this process.

拟议研究的目标是检查已确定的皮肤感觉神经元变化的时间过程。 神经元和脊髓神经元负责发展和维持炎性和 神经性疼痛状态。这些神经元在疼痛信息的处理中起着关键作用。这些研究 将实现三个具体目标。在第一个目标中，我们将采用生理和解剖相结合的方法， 技术，以确定正常小鼠的初级传入和表面背角细胞的特性。 在第二个目标中，我们将确定相同细胞在炎症性和神经性损伤后的特性。 损伤机械和热敏感性的行为测试将与 识别神经元。在第三个目标中，我们将使用两个转基因小鼠系（一个具有辣椒素/热 通道TRPV 1敲除，具有Mas基因相关的G蛋白偶联受体D（Mrgdprd） 敲除和敲入绿色荧光蛋白）。TRPV 1已被证明介导某些方面的 热敏感性，并且Mrgprd仅在皮肤感觉伤害感受器群体中发现。我们有 最近发现，这些皮肤伤害感受器在Mrgprd基因敲除小鼠，有减弱的热反应。 我们将确定这两种小鼠系的初级传入和次级伤害感受器的特性 炎症性和神经性损伤。通过比较行为和神经数据，我们将能够 评估这些遗传操作对以下疼痛状态的诱导和维持的影响： 两种伤害。在所有三个具体目标中收集的数据将用于开发神经网络模型。 在这些疼痛状态中至关重要的回路。通过比较这三组，我们希望阐明 初级传入神经元和次级伤害感受神经元的特定群体对这一过程至关重要。