Primary and Secondary Nociceptors in Persistent Pain

持续性疼痛中的初级和次级伤害感受器

基本信息

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
项目类别：
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&apos 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

项目摘要

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.

拟议的研究的目的是检查已识别皮肤感觉的变化的时间过程神经元和脊髓神经元负责发育和维持炎症和神经性疼痛状态。这些神经元在处理疼痛信息中起关键作用。这些研究将解决三个具体目标。在第一个目标中，我们将采用合并的生理和解剖学确定正常小鼠中主要传入和表面背角细胞的特性的技术。在第二个目标中，我们将确定炎症和神经性炎性后相同细胞的特性受伤。将机械和热敏感性的行为测试与在确定的神经元。在第三个目标中，我们将使用两条跨齿小鼠线（一种具有辣椒素/热量频道TRPV1被淘汰，具有与Mas-Gene相关的G蛋白偶联受体D（MRGDPRD）被敲出来，绿色荧光蛋白被撞倒）。 TRPV1已显示用于调解热敏感性和MRGPRD仅在皮肤感官伤害感受器中发现。我们有最近发现，在MRGPRD敲出小鼠中这些皮肤伤害感受器已减弱热反应。我们将确定这两种鼠标线中的主要传入和次级伤害感受器的特性炎症和神经性损伤。通过比较行为和神经数据，我们将能够评估这些遗传操纵对疼痛状态的诱导和维持的影响两种类型的伤害。在所有三个特定目标中收集的数据将用于开发神经模型在这些疼痛状态中必不可少的电路。通过比较三组，我们希望阐明特定的原发传入和继发性伤害性神经元对此过程至关重要。