Heterogeneous distribution of inhibitory inputs among motor units as a key mechanism for motor adaptations to pain

Abstract

Pain significantly influences movement, yet the neural mechanisms underlying the range of observed motor adaptations remain unclear. This study combined experimental data and in silico models to investigate the contribution of inhibitory and neuromodulatory inputs to motor unit behaviour in response to nociceptive stimulation during contractions at 30% of maximal torque. Specifically, we aimed to unravel the distribution pattern of inhibitory inputs to the motor unit pool. Seventeen participants performed isometric knee extension tasks under three conditions: Control, Pain (induced by injecting hypertonic saline into the infra-patellar fat pad), and Washout. We identified large samples of motor units in the vastus lateralis (up to 53/participant) from high-density electromyographic signals, leading to three key observations. First, while motor unit discharge rates significantly decreased during Pain, a substantial proportion of motor units (14.8-24.8%) did not show this decrease and, in some cases, even exhibited an increase. Second, using complementary approaches, we found that pain did not significantly affect neuromodulation, making it unlikely to be a major contributor to the observed changes in motor unit behaviour. Third, we observed a significant reduction in the proportion of common inputs to motor units during Pain. To explore potential neurophysiological mechanisms underlying these results, we simulated the behaviour of motor unit pools with varying distribution patterns of inhibitory inputs. Our simulations support the hypothesis that a non-homogeneous distribution of inhibitory inputs, not strictly organised according to motor unit size, is a key mechanism underlying the motor response to nociceptive stimulation during moderate contraction intensity. Key pointsO_LIPain affects movement, but the neural mechanisms underlying these motor adaptations are not well defined. C_LIO_LIThe traditional view is that pain causes uniform (homogeneous) inhibition among motor units. C_LIO_LIRecent research has observed differential motor unit responses to experimental pain - some with decreased discharge rates and others with increased discharge rates. C_LIO_LICombining experimental data with modelling, we provide compelling evidence of increased inhibition that is non-uniformly distributed across motor units, regardless of their size. C_LI Legend of the abstract figureWe combined experimental data and in silico models to investigate the contribution of inhibitory and neuromodulatory inputs to motor unit behaviour in response to nociceptive stimulation during submaximal isometric contractions at 30% of maximal voluntary contraction. We identified large samples of motor units in the vastus lateralis, leading to three key observations. First, while motor unit discharge rates significantly decreased during Pain, a substantial proportion of motor units did not show this decrease and, in some cases, even exhibited an increase. Second, using complementary approaches, we found that pain did not significantly affect neuromodulation, making it unlikely to be a major contributor to the observed changes in motor unit behaviour. Third, we observed a significant reduction in the proportion of common inputs to motor units during Pain. Together with our simulations, these results provide evidence of increased inhibition that is non-uniformly distributed across motor units, regardless of their size. Ppp, pulses per second; MVC, maximal voluntary contraction.