The aim of this human study was to investigate the relation between the experimentally induced muscle pain intensity (i.e., amount of nociceptive activity) and 1) motor unit (MU) firing decrease and 2) MU conduction velocity (CV). In 12 healthy subjects, nociceptive afferents were stimulated in the right tibialis anterior muscle by three intramuscular injections of hypertonic saline (0.2 ml, 0.5 ml, and 0.9 ml) separated by 140 seconds. The subjects performed six isometric contractions (20 s long) at 10% of the maximal voluntary contraction during the experimental muscle pain. The same set of six contractions was performed without any infusion before the painful condition on the right leg. The procedure was repeated for the left leg with infusion of isotonic (non-painful) saline. Intramuscular and surface electromyographic (EMG) signals were collected to assess MU firing rate and CV. The firing rate of the active MUs (range: 7.4-14.8 pulses per second, pps) did not change significantly in the three control conditions (without infusion for the right and left leg, and with infusion of isotonic saline in the left leg). There was, on the contrary, a significant decrease (in average, mean ± SE, 1.03 ± 0.21 pps) of the firing rates during the painful condition. Moreover, MU firing rates were inversely significantly correlated with the subjective scores of pain intensity. Single MU CV was 3.88 ± 0.03 m/s (mean ± SE, over all the MUs) with no statistical difference among any condition, i.e., the injection of hypertonic saline did not alter the muscle fiber membrane properties of the observed MUs. Progressively increased muscle pain intensity causes a gradual decrease of MU firing rates. This decrease is not associated with a change in MU membrane properties, indirectly assessed by CV. This study demonstrates a central inhibitory motor control mechanism with an efficacy correlated to the nociceptive activity.