PAINFUL DIABETIC NEUROPATHY

糖尿病是美国神经病变最常见的原因，几乎1/4的人 患者遭受慢性疼痛。疼痛性糖尿病神经病变（PDN）对糖尿病患者的生活质量有显著的不良影响。 生活质量;没有可用的治疗方法可靠地将疼痛降低到临床显著程度。 单纯疱疹病毒（HSV）天然高效靶向背根神经节的神经元 (DRG)从外周接种。在以前的研究中，我们已经证明，复制能力低下， 基于HSV的载体被工程化以表达抑制性神经递质、抗炎肽或其药学上可接受的盐。 胶质细胞衍生的神经营养因子可以减轻慢性疼痛的啮齿动物模型中的疼痛。我们提出一系列 的研究，以测试的假设，即HSV介导的基因转移到DRG，实现了皮下 该载体的接种，将提供一种新的但实用的治疗策略，用于治疗疼痛性疾病。 糖尿病神经病变。五个具体目标概述了调查的发病机制，疼痛的糖尿病 神经病变，并探讨HSV介导的基因转移可用于减少 糖尿病啮齿动物模型中的机械性痛觉过敏、机械性异常性疼痛和炎性疼痛 神经病变这些研究还将为基因治疗的发展提供临床前数据 PDN是一种通过可用的医学治疗控制不佳的病症。

Diabetes mellitus is the most common cause of neuropathy in the United States, and almost 1/4 of those patients suffer from chronic pain. Painful diabetic neuropathy (PDN) has a significant adverse effect on quality of life; none of the available treatments reliably reduce the pain to a clinically significant degree. Herpes simplex virus (HSV) naturally targets with high efficiency to neurons of the dorsal root ganglion (DRG) from peripheral inoculation. In previous studies we have demonstrated that replication incompetent HSV-based vectors engineered to express inhibitory neurotransmitters, anti-inflammatory peptides, or the glial cell derived neurotrophic factor can reduce pain in rodent models of chronic pain. We propose a series of studies to test the hypothesis that HSV-mediated gene transfer to the DRG, achieved by subcutaneous inoculation of the vector, will provide a novel yet practical therapeutic strategy for the treatment of painful diabetic neuropathy. Five specific aims are outlined to investigate the pathogenesis of painful diabetic neuropathy and to explore the possibility that HSV-mediated gene transfer can be used to reduce mechanical hyperalgesia, mechanical allodynia, and inflammatory pain in a rodent model of diabetic neuropathy. These studies will also provide preclinical data towards the development of a gene therapy approach for PDN, a condition which is poorly controlled by available medical treatments.