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

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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.