FUNCTIONAL ANALYSIS OF DISTINCT NOCICEPTOR POPULATIONS

描述（改编自申请人的摘要）：本研究的总体目标 一个建议是确定特定类别的伤害感受器，有助于两个 疼痛的主要类型有炎症性疼痛和神经损伤性疼痛。 而且我们 目的是确定发生在这些类别的伤害感受器的功能变化。 这些研究将指导新的疼痛疗法的发展， 特定的神经机制上选择群体的伤害感受器。两类 无髓鞘伤害感受器，神经化学和解剖学上不同， 最近被确认。一类是植物的同种凝集素B4， 另一类不结合同种凝集素B4，但含有神经肽并表达 神经生长因子受体。 我们有大量的初步数据， 表明这两类伤害感受器在功能上不同。 Isolectin B4阳性和阴性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 对有害热的反应（Stucky和Lewin，1999）。 一个突出的假设， 文献表明同种凝集素B4阴性的伤害感受器介导炎性 而isolectin 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。 我们的目标是利用 电生理技术，以确定是否发生功能变化 选择性地在同种凝集素B4阳性或同种凝集素B4阴性的伤害感受器中 在神经损伤或炎症中。 此外，我们将确定是否 选择性消除同种凝集素B4阳性或同种凝集素B4 负性伤害感受器减少或消除行为痛觉过敏， 发生于神经损伤或炎症。

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.