Little is known about the mechanisms leading to chronic neck-shoulder musculoskeletal disorders (MSD). The aim of the present study was to investigate and compare motor function during controlled, low load, repetitive work together with chronic or acute experimental neck-shoulder pain. The clinical study was performed on workers with (n = 12) and without (n = 6) chronic neck-shoulder pain. In the experimental study, experimental muscle pain was induced in healthy subjects by intra-muscular injection of hypertonic saline into the trapezius muscle (n = 10). The assessed parameters related to motor performance were: work task event duration, cutting forces, surface electromyogram (EMG) activity in four shoulder muscles, displacement of the centre of pressure, and arm and trunk 3D movements. For controlled cutting force levels, chronic and acute experimental pain provoked a series of changes: a decreased working rhythm and a protective reorganisation of muscle synergy (experimental study), higher EMG frequency contents which may indicate altered motor unit recruitment, and greater postural activity and a tendency towards increased arm and trunk movements. These pain-related changes can play a role in the development of MSD. The present clinical and experimental study demonstrated similar interactions between motor co-ordination and neck-shoulder pain in occupational settings. We therefore suggest that this experimental model can be used to study mechanisms related to MSD. Information on such modulatory processes may help in the design of new strategies aimed at reducing the development of MSD.