TOOLS FOR THE DISSECTION OF PAIN TRANSMISSION PATHWAYS

这项建议涉及NINDS研究主题l.E.1，“疼痛和感觉传导机制定量评估的客观方法的发展”。疼痛的传播途径对人类的行为有重大影响。它们通常是保护性的，但往往会变得病态。人们对从一个到另一个的过渡或路线调整知之甚少。为了更准确地描述正常疼痛和病理性疼痛的传导，有人建议构建一种疼痛通路的解剖工具。在成年背根神经节中，主要的伤害性感受器是表达P物质和CGRP的神经生长因子(NGF)反应神经元，以及TrkA(NGF)受体阴性的IB4凝集素结合神经元。将采用针对TrkA的靶向毒素和另一例针对IB4结合部分的靶向毒素来具体消除这些神经元类型。这将允许在相互独立的环境中对这两种神经元类型进行体外和体内研究。这些工具将导致更好地了解伤害性感受机制，并可能导致一些慢性疼痛状态的新疗法。拟议的商业应用：这项提议寻求为表达TrkA受体的神经元开发一种免疫油化工具，TrkA受体是NGF的信号转导受体。拟议的工具将为研究人员提供一种新的、创新的方法来探索NGF反应细胞在疼痛传递中的功能。商业潜力从神经科学的创新研究工具到治疗疼痛的可能疗法。

This proposal addresses NINDS Research topic l.E.1, "Development of objective methods for quantitative assessment of pain and sensory conduction mechanisms." The pathways of pain transmission have a major impact on human behavior. They are normally protective, but too often become pathological. The transition or re-routing from one to the other is poorly understood. It is proposed to construct a tool for the dissection of pain pathways, in order to delineate more precisely the transmission of normal and pathological pain. The major nociceptor classes in the adult dorsal root ganglion are the nerve growth factor (NGF)-responsive neurons that express substance P and CGRP, and the IB4 lectin-binding neurons that are TrkA (NGF)-receptor-negative. Methods will be carried out to specifically eliminate individually these neuronal types using targeted toxins directed to TrkA in one case and IB4-binding moieties in the other. This will allow study in vitro and in vivo of the two neuronal types in an environment independent of each other. These tools will result in a better understanding of nociception mechanisms and possibly result in new therapies for some chronic pain states. PROPOSED COMMERCIAL APPLICATIONS: This proposal seeks to develop an immunolesioning tool for neurons that express the TrkA receptor, the signal transduction receptor for NGF. The proposed tool would give researchers a new, innovative method for probing the function of NGF-responsive cells in pain transmission. The commercial potential spans from the innovative research tool for neuroscience to a possible therapeutic in the treatment of pain.