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活动能力并减轻常见的后遗症，例如痉挛。脊髓中的神经回路可以在没有脊髓上控制的情况下功能性地协调肌肉，这一事实促使人们采取旨在促进剩余回路可塑性的干预措施。然而，活动能力的提高仍然有限，用于治疗痉挛的药物通常可以减轻痉挛，但不能改善行走。此外，痉挛的临床测试评估单个关节，但痉挛和用于治疗痉挛的药物会影响整个肢体。因此，重要的是要确定反射通路的分布和强度，并确定反射通路在运动任务期间和功能背景下的药物如何自然调节。我们建议使用多功能力学技术来系统地识别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（目标 1）。由于已知髋部姿势等自然刺激会影响肌间神经网络，但调节影响存在争议，因此将使用力学方法来阐明髋部姿势是否影响可促进重量支撑和步态转换的神经通路（目标 2）。最后，检查反射通路的系统方法将与 α-2 激动剂（替扎尼定和可乐定）结合使用，以更好地了解它们的抗痉挛作用机制（目标 3a）和对整个肢体功能的影响（目标 3b）。目前，抗痉挛作用归因于兴奋性自生基团的抑制二、途径。已知第二组通路分布广泛，因此肌间通路也可能有助于解痉作用和不良的步行结果。这一目标将达到双重目的，即对介导抗痉挛作用的本体感觉通路进行分类，同时将研究结果置于功能背景中。将使用机器人技术通过测量肢体刚度来评估整个肢体功能。僵硬是痉挛的一个相关变量，它将肢体的机械特性和神经回路与运动功能联系起来。肢体僵硬度的测量可能是一种无创评估痉挛严重程度以及抗痉挛药物对整个肢体水平影响的创新方法。总而言之，这些实验将增强旨在恢复脊髓损伤后独立活动能力的康复策略，并将加强对痉挛的医疗管理。