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: 7224226
• 负责人: H Richard Koerber
• 金额: $ 31.76万
• 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/7224226
• 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

DESCRIPTION (provided by applicant): 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 3 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 2 trangenic mouse lines (1 that has the capsaicin/heat channel TRPV1 knocked out, 1 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 2 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 2 types of injury. The data gathered in all 3 specific aims will be used to develop a model of neural circuits that are essential during these pain states. By comparing the 3 groups, we hope to elucidate the specific populations of primary afferent and secondary nociceptive neurons crucial to this process.

描述（由申请方提供）：拟定研究的目的是检查确定的负责炎症和神经性疼痛状态发展和维持的皮肤感觉神经元和脊髓神经元变化的时间过程。这些神经元在疼痛信息的处理中起着关键作用。这些研究将涉及三个具体目标。在第一个目标中，我们将采用生理和解剖相结合的技术，以确定在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性和神经性损伤后的特性。机械和热敏感性的行为测试将与在识别的神经元中观察到的任何变化进行比较。在第三个目的中，我们将使用2个转基因小鼠系（1个具有辣椒素/热通道TRPV 1敲除，1个具有Mas基因相关的G蛋白偶联受体D（Mrgdprd）敲除和绿色荧光蛋白敲入）。TRPV 1已被证明介导热敏感性的某些方面，而Mrgprd仅在皮肤感觉伤害感受器群体中发现。我们最近发现，这些皮肤伤害感受器在Mrgprd基因敲除小鼠，有减弱的热反应。我们将确定炎症和神经性损伤后这2种小鼠系中初级传入和次级伤害感受器的特性。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2种类型损伤后疼痛状态的诱导和维持的影响。在所有3个特定目标中收集的数据将用于开发在这些疼痛状态期间必不可少的神经回路模型。通过比较3组，我们希望阐明初级传入和次级伤害性神经元的特定群体，这一过程至关重要。