Long-term depression of nociception in man: influence of varying stimulation parameters

Electrical low-frequency stimulation (LFS) of spinal afferents induces long-term depression (LTD) of nociceptive processing in rodents. LTD and its parameters in man are largely unknown. This study aimed to obtain the most effective design in man by varying stimulation frequency (0.5, 1, 2 Hz), number of pulses (300, 600, 1200), stimulation intensity related to pain threshold (I_p) (1-I_p, 2-I_p, 4-I_p), and by applying repetitive LFS. One hundred and twenty electrophysiological and psychophysical experiments were performed in 29 healthy volunteers. Painful electrical test stimulation and conditioning LFS were applied to right hand dorsum. Somatosensory evoked cortical potentials (SEP) were recorded and volunteers were asked to rate stimulus intensity. LFS with 0.5, 1 or 2 Hz induced significant reduction of SEP and pain ratings as compared to control group. Effect on SEP amplitude after 1 Hz LFS preponderated that of 2 Hz stimulation. LTD of SEP and pain perception was induced by noxious LFS with 300 to 1200 pulses. SEP suppression augmented with increasing number of pulses. LFS with intensities 2-I_p and 4-I_p evoked sustained depression of SEP and pain perception in comparison to control and 1-I_p LFS. Established LTD after single LFS was amplified by additional LFS. Hence this study provides evidence for LTD of spinal nociceptive processing in man and indicates a stimulation paradigm with 1 Hz, 1200 pulses and 4-I_p as most effective for induction of LTD in man.