Assessment of the Influence of Central Sensitization on the Structure and Function of the Spinal Cord and its Supplied Muscles

这项建议侧重于评估实验诱导的神经可塑性对脊髓及其供应的肌肉及其相互作用的影响。辣椒素诱导的中枢敏化(CSens)将作为一种新的实验方法来研究神经可塑性对骨骼肌和脊髓腹角的影响。研究的新颖性还包括同时记录肌电(EMG)、定量超声(QUS)和局部生化环境的变化，并与受影响肌肉的组织学相关联。脊髓背角内CSens的传入效应已被广泛研究，但对运动单位和腹角的传出效应尚未见报道。这项研究计划解决了这一巨大的知识鸿沟。5年计划目标：在健康的人类志愿者(年龄20-45岁)中，性别均衡：1.评估实验诱导的CSEN对个体运动单位兴奋性的影响，以及在自愿运动开始时第一个招募运动单位的招募模式。2.在实验诱导的CSens之间的神经节段中，建立关于运动单位的募集模式和骨骼肌性能的时间相关性，通过(A)收缩区域微环境中的生化反应；(B)收缩肌节的发生率和一致性；以及(C)使用QUS和力量稳定性来测量肌肉收缩模式。3.使用止血带诱导的缺血，评估周围神经感觉输入的可逆性减少对单个运动单位的兴奋性、募集和力量产生的影响。4.评估实验诱导的CSens对单个运动单位的兴奋性、其募集模式和双侧神经节段的力量产生的时间关系。这项NSERC建议的长期愿景和使命促进了我们对CSens影响中枢神经系统的神经可塑性、肌肉功能和局部生化环境中的相互作用的机制的理解。然后，这些方法将被用来非侵入性地测量CSens对神经肌肉变化的影响，这些变化与性别、运动、静止和营养/营养挑战有关。科学方法概述：使用一种新的实验方法，在不同浓度的CSens(兴奋)和缺血(抑制)下，将产生不同数量的感觉输入到脊髓背角，这将导致不同数量的神经可塑性。在CSENS中，将在不同的时间点同时记录受累骨骼肌的EMG、QUS和生化环境。相关和相干分析将比较肌电数据、QUS数据和收缩区域内的细胞因子浓度。最后，CSens收缩区域的肌肉活检将与对照部位进行比较，以了解收缩肌节的流行率和一致性。

This proposal focuses on evaluating the effects of experimentally induced neuroplasticity on the spinal cord, its supplied muscle and their interactions. Capsaicin induced central sensitization (CSens) will be used as a novel experimental approach to study the effects of neuroplasticity on skeletal muscle and the ventral horn of the spinal cord. Research novelty also involves the simultaneous recording of electromyography (EMG), quantitative ultrasound (QUS) and local changes in biochemical milieu in correlation with histology of the affected muscle. The afferent effects of CSens within the dorsal horn of the spinal cord has been extensively studied but the efferent effects on the motor unit and ventral horn have not. This research program addresses this critically large knowledge gap. Objectives of 5 year program: In healthy human volunteers (ages 20-45), balanced for sex: 1. Assess the impact of experimentally induced CSens on individual motor unit excitability and the recruitment patterns on the first recruited motor units during voluntary movement initiation. 2. Establish temporal correlations in a neuromeric segment between experimentally induced CSens on recruitment patterns of motor units and skeletal muscle performance measured by (a) biochemical responses in the microenvironment of the contractile region; (b) the prevalence and uniformity of contracted sarcomeres; and (c) muscle contraction patterns using QUS and force steadiness. 3. Using tourniquet induced ischemia, assess the reversible reduction of sensory input in a peripheral nerve on individual motor unit excitability, recruitment, and force production. 4. Assess the temporal relationship of experimentally induced CSens on the excitability of individual motor units, their recruitment patterns and force production in bilateral neuromeric segments. The long-term vision and mission of this NSERC proposal advances our understanding of the mechanisms by which CSens affects neuroplasticity of the central nervous system, muscle function and the interactions in local biochemical milieux. These approaches will then be used to noninvasively measure the effects of CSens on neuromuscular changes with regards to sex, exercise, immobility, and nutrient/nutraceutical challenges. Summary of Scientific Approach: Different amounts of sensory input to the dorsal horn of the spinal cord will be created using a novel experimental approach with different concentrations of CSens (excitation) and ischemia (inhibition) which will cause different amounts of neuroplasticity. During CSens, simultaneous recordings of EMG, QUS, and biochemical milieu of involved skeletal muscles will be sampled at various time points. Correlation and coherence analyses will compare EMG data, QUS data and cytokine concentrations within the contractile region. Finally, muscle biopsy of the CSens contractile region will be compared to a control site for the prevalence and uniformity of contracted sarcomeres.