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

中枢敏化对脊髓及其所供应肌肉的结构和功能影响的评估

• 批准号: RGPIN-2022-05370
• 负责人: Kumbhare, Dinesh
• 金额: $ 2.33万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=757865
• 关键词: Assessment; Influence; Central; Sensitization; Structure

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.

本研究的重点是评估实验诱导的神经可塑性对脊髓、其供应肌及其相互作用的影响。辣椒素诱导的中枢致敏（CSens）将作为研究神经可塑性对骨骼肌和脊髓前角影响的一种新的实验方法。研究的新颖性还包括同时记录肌电图（EMG）、定量超声（QUS）和与受影响肌肉组织学相关的局部生化环境变化。脊髓背角内CSens的传入作用已被广泛研究，但对运动单元和腹角的传出作用尚未研究。这个研究项目解决了这一巨大的知识鸿沟。5年计划目标：健康人类志愿者（年龄20-45岁），性别平衡；评估实验诱导的CSens对个体运动单元兴奋性的影响，以及在自主运动启动期间首次招募的运动单元的招募模式。2. 通过(a)收缩区微环境中的生化反应，在实验诱导的CSens与运动单元招募模式和骨骼肌表现之间的神经节段建立时间相关性；(b)挛缩肌瘤的普遍性和统一性；(c)使用QUS和力稳定性的肌肉收缩模式。3. 利用止血带诱导的缺血，评估周围神经感觉输入的可逆减少对个体运动单元兴奋性、恢复和力产生的影响。4. 评估实验诱导的CSens与单个运动单元的兴奋性、它们的招募模式和双侧神经节段的力产生的时间关系。这项NSERC提案的长期愿景和使命是促进我们对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。这些方法将被用于无创测量CSens对神经肌肉变化的影响，这些变化与性别、运动、不动和营养/营养品挑战有关。科学方法总结：使用一种新的实验方法，通过不同浓度的CSens（兴奋）和缺血（抑制），将产生不同数量的脊髓背角感觉输入，这将导致不同数量的神经可塑性。在CSens过程中，将在不同的时间点采样相关骨骼肌的肌电图、QUS和生化环境的同时记录。相关和相干分析将比较肌电图数据，QUS数据和收缩区域内的细胞因子浓度。最后，将CSens收缩区的肌肉活检与对照部位进行比较，以了解收缩肌节的患病率和均匀性。