FUNCTIONAL ANALYSIS OF DISTINCT NOCICEPTOR POPULATIONS

描述（改编自申请人的摘要）：本项目的总体目标 提议是确定特定类别的伤害感受器，这些感受器有助于两种 疼痛的类型主要有炎性疼痛和神经损伤性疼痛。 此外，我们 旨在识别这些类别的伤害感受器中发生的功能变化。 这些研究将指导针对目标的新型疼痛疗法的开发 特定伤害感受器群体的特定神经机制。两类 无髓鞘伤害感受器在神经化学和解剖学上有所不同， 最近被识别。一类发现植物异凝集素 B4，而 另一类不结合异凝集素 B4，但含有神经肽并表达 神经生长因子受体。 我们有大量初步数据表明 表明这两类伤害感受器在功能上是不同的。 同凝素 B4 正负伤害感受器具有不同的动作电位 特征，不同密度的Na通道并表现出不同的 对有害热量的反应（Stucky 和 Lewin，1999）。 一个突出的假设是 文献称异凝集素 B4 阴性伤害感受器介导炎症 疼痛，而异凝集素 B4 阳性伤害感受器介导神经损伤疼痛。 然而，这一假设尚未得到检验。 我们的目标是使用 电生理技术来确定功能是否发生变化 选择性作用于异凝集素 B4 阳性或异凝集素 B4 阴性伤害感受器 在神经损伤或炎症期间。 此外，我们将确定是否 选择性消除异凝集素 B4 阳性或异凝集素 B4 负性伤害感受器减少或消除行为痛觉过敏 与神经损伤或炎症有关。

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.