DORSAL SPINAL CORD STIMULATION--VASODILATOR MECHANISMS

背侧脊髓刺激——血管舒张机制

• 批准号: 6187927
• 负责人: ROBERT D FOREMAN
• 金额: $ 14.3万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6187927
• 关键词: afferent nerve; antidromic impulse; blood vessel disorder; calcitonin gene related peptide; dorsal column; electrostimulus; evoked potentials; excitatory aminoacid; gamma aminobutyrate; laboratory rat; neurotransmitter antagonist; nonhuman therapy evaluation; peripheral blood vessel; physical therapy; skin circulation; spinal cord; substance K; substance P; sympathetic nervous system; ultrasound blood flow measurement; vascular endothelium permeability; vascular smooth muscle nervous control; vasodilators

DESCRIPTION (Adapted from the applicant's abstract): Electrical stimulation of the dorsal spinal cord (SCS) is used to provide pain relief in patients with peripheral vascular disease (PVD). Clinical and basic science studies indicate that the beneficial effect of SCS in PVD is associated with increased blood flow to the extremities. Previous work from the applicant's laboratory has demonstrated that SCS-induced vasodilation is mediated by antidromic activation of primary afferent neurons resulting in release of a vasodilator peptide from peripheral sensory nerve endings. The overall goal of this proposal is to investigate the antidromic mediated mechanisms involved in the peripheral vascular responses to SCS. Four Specific Aims are proposed to address this hypothesis. In Specific Aim 1 the investigators will test the hypothesis that antidromic release of vasoactive peptides is the primary mechanism of SCS-induced vasodilation at clinically relevant intensities. This protocol will be examined in anesthetized and in conscious, freely moving animals. Specific Aim 2 will test the hypothesis that SCS-induced antidromic activation of afferent nerves can be directly demonstrated through measurement of increased electrical activity in sensory nerves. This protocol involves assessment of afferent nerve activity in response to SCS. In Specific Aim 3 the investigators will test the hypothesis that the antidromic mediated effects of SCS produce increased vascular permeability, and the increased permeability is due to activation of neurokinin-1 receptors by Substance P release from sensory nerve endings in the peripheral vasculature. This protocol involves assessment of changes in peripheral vascular permeability through examination of Evan's blue extravasation and translocation of Monastral blue from intravascular to extravascular spaces. The investigators also will examine the contribution of calcitonin gene-related peptide on permeability changes due to SCS. In Specific Aim 4 they hypothesize that the antidromic effects of SCS require activation of synaptic pathways in the spinal cord. This protocol addresses the peripheral vasodilator effects of SCS before and after intraspinal microinjection of pharmacological antagonists of gamma-aminobutyric acid and excitatory amino acids. Results of the overall investigation will further define the antidromic effects of SCS related to peripheral vascular mechanisms and spinal pathways involved in eliciting this effect. The results also will demonstrate the importance of using SCS as a tool to investigate the effects of antidromic-induced release of vasoactive substances from sensory nerve endings. Ultimately, information obtained from these studies has potential clinical application not only to peripheral vascular disease but also to diverse processes such as wound healing, tissue inflammation, angina pectoris, autonomic dysreflexia and Raynaud's phenomenon.

描述（改编自申请人摘要）：电刺激 背侧脊髓（SCS）用于缓解患者的疼痛， 外周血管疾病（PVD）。临床和基础科学研究表明 SCS在PVD中的有益作用与增加血液 流向四肢申请人实验室的先前工作 证明SCS诱导的血管舒张是由逆向激活介导的 的初级传入神经元，导致血管舒张肽的释放， 外周感觉神经末梢。本提案的总体目标是 研究外周血淋巴细胞中参与的逆向介导机制， 对SCS的血管反应。为解决这一问题，提出了四个具体目标 假说.在具体目标1中，研究人员将检验以下假设： 血管活性肽的逆向释放是 临床相关强度的SCS诱导的血管舒张。本方案将 在麻醉和有意识的自由活动的动物中进行检查。具体 目的2将检验SCS诱导的逆向激活的假设， 传入神经可以通过测量增加的 感觉神经的电活动。本方案涉及评估 传入神经活动对SCS的反应。在《特定目标3》中，研究人员 将检验SCS的逆向介导效应产生 增加的血管渗透性，增加的渗透性是由于 感觉神经释放P物质激活神经激肽-1受体 末梢血管本方案涉及评估 伊文思蓝法检测外周血管通透性的变化 单星蓝从血管内外渗和移位到 血管外间隙调查人员还将研究 降钙素基因相关肽对SCS引起的渗透性变化的影响。在特定 他们假设SCS的逆行效应需要激活 脊髓中的突触通路。该协议针对外围设备 脊髓内微量注射盐酸二甲双胍前后脊髓刺激的扩血管作用 γ-氨基丁酸和兴奋性氨基的药理学拮抗剂 acids.全面调查的结果将进一步确定逆行 与外周血管机制和脊髓通路相关的SCS效应 参与了引发这种效应。结果还将证明， 使用SCS作为工具来调查 感觉神经末梢的血管活性物质的逆向诱导释放。 最终，从这些研究中获得的信息具有潜在的临床意义 不仅适用于外周血管疾病， 例如伤口愈合、组织炎症、心绞痛 自主神经反射障碍和雷诺现象。