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

描述(申请人提供)：脊髓损伤后康复的一个目标是恢复活动能力并减轻常见的后遗症，如痉挛。脊髓中的神经回路可以在功能上协调肌肉，而不需要脊柱上的控制，这一事实促使人们采取干预措施，旨在促进剩余回路的可塑性。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，但不能改善行走。此外，痉挛的临床测试评估单个关节，但痉挛和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在功能背景下如何受到药物的自然调节。我们建议使用通用的机械成像技术来系统地识别连接主要后肢肌群的肌间反射网络的分布、强度和时间进程(目标1)。由于髋部姿势等自然刺激已知会影响肌肉间神经网络，但这种调节影响存在争议，因此将使用机械学方法来阐明髋部姿势是否会影响可能促进重量支持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，抗痉挛作用主要归因于抑制兴奋性自生性基团。 II路径。众所周知，第二类通路分布广泛，因此肌肉间通路也可能导致解痉挛效果和较差的步行效果。这一目的将服务于双重目的，即对调节解痉挛效应的本体感觉通路进行分类，同时也将发现放在功能的背景下。通过使用机器人技术测量肢体硬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在一起。肢体僵硬的测量可能是一种创新的方法，可以无创地评估痉挛程度和整个肢体水平抗痉挛药物的影响。总而言之，这些实验将加强旨在恢复脊髓损伤后独立活动的康复策略，并将加强对痉挛的医疗管理。

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.