FUNCTIONAL ANALYSIS OF DISTINCT NOCICEPTOR POPULATIONS

描述(改编自申请人的摘要)：这项工作的总体目标 提案是确定特定类别的伤害性感受器，它们对两种 主要疼痛类型有炎症性疼痛和神经损伤痛。此外，我们 目的确定这类伤害性感受器的功能变化。 这些研究将指导针对以下目标的新型疼痛疗法的开发 伤害性感受器特定群体的特定神经机制。两个班级 在神经化学和解剖学上不同的无髓鞘伤害性感受器有 最近被确认身份。一类发现了植物异凝素B4，而 其他类不结合异凝素B4，但含有神经肽并表达 神经生长因子受体。我们有大量的初步数据表明 证明这两类伤害性感受器在功能上是不同的。 Isolectin B4阳性和阴性伤害性感受器具有不同的动作电位 特性，不同密度的钠通道，表现出明显的不同 对有害高温的反应(Stucky和Luin，1999)。中的一个重要假说 文献表明，异凝素B4阴性的伤害性感受器介导炎症。 疼痛，而异凝素B4阳性的伤害性感受器介导神经损伤性疼痛。 然而，这一假设尚未得到检验。我们的目标是利用 用于确定是否发生功能改变的电生理技术 选择性地在异凝素B4阳性或异凝素B4阴性的伤害性感受器中 在神经损伤或炎症期间。此外，我们将确定是否 选择性消除异凝素B4阳性或异凝素B4 负性伤害性感受器减少或消除行为痛觉过敏 伴随神经损伤或炎症而发生。

DESCRIPTION (adapted from applicant's abstract): The overall goal of this proposal is to identify specific classes of nociceptors that contribute to two major types of pain, inflammatory pain and nerve injury pain. Furthermore, we aim to identify functional changes that occur in these classes of nociceptors. These studies will direct the development of novel pain therapies that target specific neural mechanisms on select populations of nociceptors. Two classes of unmyelinated nociceptors, which differ neurochemically and anatomically, have recently been identified. One class finds the plant isolectin B4 whereas the other class does not bind isolectin B4 but contains neuropeptides and expresses receptors for nerve growth factor. We have substantial preliminary data that show that these two classes of nociceptors are functionally distinct. Isolectin B4 positive and negative nociceptors have different action potential characteristics, different densities of Na+ channels and exhibit distinct responses to noxious heat (Stucky and Lewin, 1999). A prominent hypothesis in the literature is that isolectin B4 negative nociceptors mediate inflammatory pain whereas isolectin B4 positive nociceptors mediate nerve injury pain. However, this hypothesis has not been tested. Our goal is to use electrophysiological techniques to determine whether functional changes occur selectively in isolectin B4 positive or isolectin B4 negative nociceptors during nerve injury or inflammation. Furthermore, we will determine whether selective elimination of isolectin B4 positive or isolectin B4 negative nociceptors reduces or eliminates the behavioral hyperalgesia that occurs with nerve injury or inflammation.