Influence of alpha-2 agonists on reflex pathways and limb stiffness

α2激动剂对反射通路和肢体僵硬的影响

基本信息

批准号：
8827431
负责人：
Mark A Lyle
金额：
$ 4.72万
依托单位：
GEORGIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8827431
关键词：
3-Dimensional Address Affect Biological Neural Networks Clinical Clonidine Disease Distal Drug usage Effectiveness Ensure Felis catus Flexor Foot-drop Future Gait Goals Grouping Health Hindlimb Hip Joint Hip region structure Human Individual Interneurons Intervention Joints Knee Learning Limb structure Link Maps Measurement Mechanics Mediating Medical Methods Monitor Motor Muscle Neural Pathways Organ Outcome Pathway interactions Patient Care Persons Pharmaceutical Preparations Phase Posture Property Rattus Reflex action Rehabilitation therapy Research Research Training Robotics Role Severities Spasm Spinal Spinal Cord Spinal Injuries Spinal cord injury Stimulus Techniques Technology Testing Therapeutic Time Training Walking Weight Work alpha 2 agonist base clinical care improved innovation insight limb movement neural circuit neurophysiology neuroregulation novel rectus femoris rehabilitation strategy relating to nervous system research study response sensory feedback tibialis anterior muscle tizanidine treatment effect

项目摘要

DESCRIPTION (provided by applicant): A goal of rehabilitation after spinal cord injury is to restore mobility and mitigate common sequalae such as spasticity. The fact that neural circuitry in the spinal cord can functionally coordinate muscles without supraspinal control has prompted interventions intended to promote plasticity of remaining circuitry. Gains in mobility remain limited, however, and medications used to treat spasticity generally reduce spasms but do not improve walking. In addition, clinical tests for spasticity assess individual joints, yet spasticit and the drugs used to treat it affect the whole limb. It is important therefore to identify the distribution and strength of reflex pathways, and determine how reflex pathways are naturally modulated during motor tasks and by medications in a functional context. We propose to use the versatile mechanographic technique to systematically identify the distribution, strength, and time course of intermuscular reflex networks linking major hindlimb muscle groups (Aim 1). Because natural stimuli such as hip posture are known to influence intermuscular neural networks but the modulatory influence is controversial, the mechanographic approach will be used to clarify whether hip posture affects neural pathways that could promote weight support and gait transitions (Aim 2). Lastly, the systematic approach for examining reflex pathways will be used in combination with alpha-2 agonists (tizanidine and clonidine) to better understand their antispasticity mechanisms of action (Aim 3a) and influence on whole limb function (Aim 3b). Currently, the antispastic effects are attributed to suppression of excitatory autogenic group II pathways. Group II pathways are known to be widely distributed and therefore intermuscular pathways could also contribute to the antispastic effect, and the poor walking outcomes. This aim will serve the dual purpose of classifying the proprioceptive pathways that mediate the antispastic effect while also placing the findings in a functional context. Whole limb function wil be evaluated by the measurement of limb stiffness using robotic technology. Stiffness is a relevant variable for spasticity that links mechanical properties of the limb and neural circuits t motor function. The measurement of limb stiffness could be an innovative way to noninvasively assess spasticity severity and the influence of antispastic medications at the whole limb level. Taken together, these experiments will enhance rehabilitation strategies intended to restore independent mobility after spinal cord injury and will enhance the medical management for spasticity.

描述（由申请人提供）：脊髓损伤后康复的目标是恢复迁移率并减轻诸如痉挛之类的常见序列。脊髓中的神经回路可以在没有脊柱上部控制的情况下在功能上进行肌肉进行辅助，这促使干预措施旨在促进剩余电路的可塑性。然而，活动能力的提高仍然有限，用于治疗痉挛的药物通常会减少痉挛，但不能改善步行。此外，痉挛的临床测试评估了各个关节，但是痉挛和用于治疗其治疗的药物会影响整个肢体。因此，重要的是要确定反射途径的分布和强度，并确定反射途径在运动任务期间和通过功能背景下的药物进行自然调节。我们建议使用多功能机械学技术系统地确定连接主要后肢肌肉群的肌间反射网络的分布，强度和时间过程（AIM 1）。由于已知自然刺激（例如髋关节姿势）会影响肌间神经网络，但调节作用是有争议的，因此将使用机械方法来阐明髋关节姿势是否影响可以促进体重支持和步态过渡的神经途径（AIM 2）。最后，检查反射途径的系统方法将与Alpha-2激动剂（Tizanidine和Clonidine）结合使用，以更好地理解其反疾病的作用机制（AIM 3A）和对整肢功能的影响（AIM 3B）。目前，抗动物作用归因于抑制兴奋性自源组 II途径。已知II组途径被广泛分布，因此肌间途径也可能导致反刺激性效应，并且步行效果不佳。该目标将达到双重目的，即分类介导反弹效应的本体感受途径，同时还将发现放置在功能环境中。将通过使用机器人技术测量肢体刚度来评估整个肢体功能。刚度是痉挛的相关变量，该变量将肢体和神经回路的机械性能T运动功能联系起来。肢体僵硬度的测量可能是一种创新的方法，可以无创地评估痉挛性严重程度和整个肢体水平上的抗鼻素药物的影响。综上所述，这些实验将增强旨在恢复脊髓损伤后独立移动性的康复策略，并将增强医疗管理的痉挛。