TOOLS FOR THE DISSECTION OF PAIN TRANSMISSION PATHWAYS

本提案涉及NINDS研究课题l.E.1，“开发量化评估疼痛和感觉传导机制的客观方法”。疼痛传递的途径对人类行为有重要影响。它们通常是保护性的，但往往变得病态。从一个到另一个的转换或重新路由很少被理解。为了更准确地描述正常疼痛和病理性疼痛的传递，建议构建一个疼痛路径解剖工具。成人背根神经节中的主要伤害感受器类别是表达P物质和CGRP的神经生长因子（NGF）反应神经元和TrkA （NGF）受体阴性的IB4凝集素结合神经元。研究人员将使用针对TrkA和ib4结合部分的靶向毒素分别特异性消除这些神经元类型。这将允许在相互独立的环境中进行两种神经元类型的体外和体内研究。这些工具将导致更好地理解伤害感觉机制，并可能导致一些慢性疼痛状态的新疗法。拟议的商业应用：该提案旨在开发一种免疫定位工具，用于表达TrkA受体（NGF的信号转导受体）的神经元。该工具将为研究人员提供一种新的、创新的方法来探测ngf反应细胞在疼痛传递中的功能。其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.