Functional and histological changes to peripheral innervation following spinal cord stimulation in patients with painful diabetic neuropathy

项目摘要 糖尿病是周围神经病变的最常见原因，这种疾病影响了3000多万美国人。 通常，这种情况下发生的痛苦糖尿病周围神经病变（PDPN），这是特别具有挑战性的 在临床上进行治疗，部分原因是缺乏有效的治疗方法和依赖阿片类镇痛药的风险。 脊髓刺激（SCS）是一种刺激脊柱神经电活动的治疗方法， 有效治疗疼痛疾病，包括PDPN，SCS现已通过多种器械获得FDA批准 厂商然而，SCS改善疼痛的机制尚不清楚，可能涉及 促进神经可塑性和小纤维神经再生。我们假设大脑中的电活动 SCS治疗刺激脊神经可改善疼痛，这是由于外周神经功能的改善，或与外周神经功能的改善平行。 组织神经支配这是基于几十年的研究证据，电刺激可以促进神经 可塑性和再生我们将在18个月纵向研究中比较3个PDPN治疗组（每组N=15） 研究：传统医疗管理（CMM）、SCS治疗或SCS延迟激活器械 术后3个月（以控制手术或器械植入的安慰剂效应）。一个由以下人员组成的团队 神经科学家、神经学家、神经调节外科医生和计算/生物统计学专家将收集一个 8-本研究时间轴上的点数据集，以便严格比较疼痛改善评分， 以及大纤维神经病变评估、生活质量评分和代谢参数。的创新之处 研究进一步推动了包括一个新的功能测量小纤维神经电活动，使用 检测早期神经病变（DEN）设备，该设备采用微针阵列来收集神经数据 活动从皮肤表面4 mm深。这是第一个能够测量小神经纤维的设备 活性作为小纤维周围神经病变如糖尿病性神经病变的诊断试验。综合起来看， 这项研究将提供关于SCS治疗改善PDPN的重要新数据，以及其机制是否 包括小纤维组织神经支配或神经活动变化。

PROJECT ABSTRACT Diabetes is the most common cause of peripheral neuropathy, a condition that impacts over 30 million Americans. Often, this condition occurs as painful diabetic peripheral neuropathy (PDPN), which is particularly challenging to treat in the clinic, in part due to the lack of effective treatments and the risk of dependency for opioid analgesics. Spinal cord stimulation (SCS) is a treatment that stimulates nerve electrical activity in the spine, and is proven to be effective for pain conditions, including PDPN, for which SCS is now FDA approved through multiple device manufacturers. However, the mechanisms by which SCS improves pain are not yet known, and may involve promoting neural plasticity and small fiber nerve regeneration. We hypothesize that the electrical activity in stimulated spinal nerves with SCS treatment improves pain due to, or in parallel to, improvements in peripheral tissue innervation. This is based on decades of research evidence that electrical stimulation can promote nerve plasticity and regeneration. We will compare 3 PDPN treatment groups (N=15 each) across an 18mo longitudinal study: conventional medical management (CMM), SCS treatment, or SCS with a delayed activation of the device at 3mo post-surgery (to control for placebo effect of the surgery or device implantation). A team comprised of neuroscientists, neurologists, a neuromodulation surgeon, and computational/biostatistical experts will collect an 8-point dataset across this study timeline, in order to rigorously compare pain improvement scores with small and large fiber neuropathy assessments, quality of life scores, and metabolic parameters. The innovation of this study is further driven by the inclusion of a new functional measure of small fiber nerve electrical activity, using the Detecting Early Neuropathy (DEN) device, which employs a microneedle array to collect data on nerve activity up to 4mm deep from the skin surface. This is the first device capable of measuring small nerve fiber activity as a diagnostic test for small fiber peripheral neuropathy, such as diabetic neuropathy. Taken together, this study will provide important new data on PDPN improvements with SCS treatment and whether mechanisms include changes to small fiber tissue innervation or nerve activity.