Primary and Secondary Nociceptors in Persistent Pain

拟议研究的目标是检查已识别的皮肤感觉变化的时间进程。 神经元和脊髓神经元负责发展和维持炎性和 神经病理性疼痛状态。这些神经元在处理疼痛信息方面起着关键作用。这些研究 将解决三个具体目标。在第一个目标中，我们将结合生理学和解剖学 测定正常小鼠初级传入细胞和浅背角细胞特性的技术。 在第二个目标中，我们将确定炎症和神经病变后相同细胞的特性 受伤。机械和热敏性的行为测试将与在 辨认出神经元。在第三个目标中，我们将使用两个转基因小鼠品系(其中一个含有辣椒素/辣味 通道TRPV1被敲除，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)。TRPV1已被证明在某些方面调节 热敏感，而MRGPrd仅在皮肤感受性伤害性感受器中发现。我们有 最近发现，在mrgprd基因敲除小鼠中，这些皮肤伤害性感受器可以减弱热反应。 我们将确定这两个品系小鼠的初级传入和次级伤害性感受器的特性 在炎症性和神经性损伤之后。通过比较行为和神经数据，我们将能够 评估这些基因操作对以下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被用来开发神经模型 在这些疼痛状态下必不可少的回路。通过对这三个群体的比较，我们希望能阐明 初级传入神经元和次级伤害性感觉神经元的特定群体对这一过程至关重要。

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.