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

本研究的重点是评估实验诱导的神经可塑性对脊髓及其供应肌肉的影响以及它们之间的相互作用。辣椒素诱导的中枢敏感化（CSens）是研究神经可塑性对骨骼肌和脊髓前角影响的新方法。研究新颖性还涉及同时记录肌电图（EMG），定量超声（QUS）和与受影响肌肉组织学相关的生化环境中的局部变化。CSens在脊髓背角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还没有。这项研究计划解决了这一巨大的知识差距。5年计划的目标：在健康人类志愿者（年龄20 - 45岁）中，性别平衡：1。评估实验诱导的CSens对个体运动单位兴奋性的影响，以及自主运动启动期间第一次招募运动单位的招募模式。2.在神经节段中建立实验诱导的CSens对运动单位募集模式和骨骼肌性能的时间相关性，通过（a）收缩区微环境中的生化反应;（B）收缩肌节的普遍性和均匀性;以及（c）使用QUS和力稳定性的肌肉收缩模式来测量。3.使用止血带诱导的缺血，评估外周神经中感觉输入对单个运动单位兴奋性、募集和力产生的可逆性减少。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产生的时间关系。NSERC提案的长期愿景和使命促进了我们对CSens影响中枢神经系统神经可塑性、肌肉功能和局部生化环境相互作用的机制的理解。然后，这些方法将用于非侵入性地测量CSens对神经肌肉变化的影响，包括性别，运动，不动性和营养/营养品挑战。科学方法概述：将使用具有不同浓度的CSens（兴奋）和缺血（抑制）的新实验方法来产生对脊髓背角的不同量的感觉输入，这将引起不同量的神经可塑性。在CSens期间，将在不同时间点对受累骨骼肌的EMG、QUS和生化环境进行同步记录。相关性和一致性分析将比较收缩区域内的EMG数据、QUS数据和细胞因子浓度。最后，将CSens收缩区域的肌肉活检与对照部位的收缩肌节的患病率和均匀性进行比较。

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.