This study in humans tested the hypothesis that nociceptive muscle afferent input facilitates the occurrence of muscle cramps. In 13 healthy adults, muscle cramps were experimentally induced in the foot by stimulating the tibialis posterior nerve at the ankle with 2-s bursts of stimuli separated by 30 s, with stimulation frequency increasing by 2-Hz increments from 10 Hz until the cramp appeared. The minimum stimulation frequency that induced the cramp was defined "cramp frequency threshold". In 2 days, elicitation of the cramp was performed in the two-feet with and without (baseline condition) injection of hypertonic (painful condition) or isotonic (control condition) saline into the deep midportion of the flexor hallucis brevis muscle, from where surface EMG signals were recorded. The cramp frequency threshold was lower for the painful condition with respect to its baseline (mean +/- SE, hypertonic saline: 25.7 +/- 2.1 Hz, corresponding baseline: 31.2 +/- 2.8 Hz; P < 0.01) while there was no difference between the threshold with isotonic injection with respect to baseline. EMG average rectified value and power spectral frequency were higher during the cramp than immediately before the stimulation that elicited the cramp (pre-cramp: 13.9 +/- 1.6 muV and 75.4 +/- 3.8 Hz, respectively; post-cramp: 19.9 +/- 3.2 muV and 101.6 +/- 6.0 Hz; P < 0.05). The results suggest that nociceptive muscle afferent activity induced by injection of hypertonic saline facilitates the generation of electrically elicited muscle cramps.