Targeting Neurons Involved in Chronic Pain Transmission

描述(摘自申请者的摘要)：慢性疼痛是一种巨大的 美国的问题：估计有3000万到1亿人 受苦受罪。通常，目前的治疗方法是无效的，而且 患者经常被描述为“服务不足”。根据最近的数据， 慢性疼痛通过P物质受体表达的神经元传递 脊髓的后角。这些神经元的消除终止于 慢性疼痛信号在几种大鼠模型中的传递。不过，这个 方法依赖于脊髓神经元的死亡。另一种方法是 维持神经系统的完整性只会破坏 这些神经元的活动。这可以通过内部化来实现 分子进入P物质受体表达神经元，干扰 传递慢性疼痛信号的能力。在此阶段I中提出了 应用程序演示了一种表达系统，用于表达 可以导致这种破坏的分子可以内化到P物质中 受体表达神经元，能表达一种标志性蛋白-绿色荧光 蛋白。这一申请的成功可能会导致解决 干扰慢性疼痛治疗的严重问题。 建议的商业应用： 这一提议将导致开发一种表达系统，用于在内部操纵细胞以扰乱或改变其功能。这样的系统将在科学研究中有很多应用，不仅在慢性疼痛方面，而且在科学家试图改变细胞过程的任何领域都有应用。此外，一种可以减弱而不是破坏细胞功能的表达系统在疾病治疗中将有很大的可能性。

DESCRIPTION (Adapted from applicant's abstract): Chronic pain is an enormous problem in the United States: it is estimated that 30 to 100 million people suffer from it. Often, current treatments are ineffective and the population of sufferers is often described as "under-served." According to recent data, chronic pain is transmitted through the Substance P receptor-expressing neurons of the dorsal horn of the spinal cord. Elimination of these neurons terminates transmission of the chronic pain signal in several rat models. However, this method relied on the death of spinal cord neurons. An alternative method that would maintain the integrity of the neuronal system would be to only disrupt the activities of these neurons. This could be achieved by internalizing molecules into Substance P receptor-expressing neurons that interfere with the ability to transmit the chronic pain signal. It is proposed in this Phase I application to demonstrate that an expression system, useful for expressing molecules that can cause this disruption, can be internalized into Substance P receptor-expressing neurons and can express a marker protein, green fluorescent protein. The success of this application could result in the resolution of serious problems that interfere with the treatment of chronic pain. PROPOSED COMMERCIAL APPLICATION: This proposal will result in the development of an expression system for use in internally manipulating cells to disrupt or alter their function. Such a system would have many applications in scientific research, not only in chronic pain, but in any area where scientists seek to alter cell processes. Additionally, an expression system that can diminish rather than destroy a cell's function would have great possibility in the treatment of disease.