Facilitation and inhibition of withdrawal reflexes following repetitive stimulation: electro- and psychophysiological evidence for activation of noxious inhibitory controls in humans

A systematic evaluation of nociceptive withdrawal reflexes and pain rating was undertaken in order to explore the mechanisms underlying temporal summation of repetitive electrocutaneous stimulation in healthy individuals (n=12; age=27.5 ± 1.5 years). Five-second subreflex threshold (RT) electrocutaneous stimulation at different frequencies (single stimulus, 5, 10, and 20 Hz) and intensities (0.6RT and 0.8RT) was applied on the dorsum of the foot, and the withdrawal reflex from the ipsilateral biceps femoris muscle was measured. The subjects scored the pain intensity on a visual analogue scale (0-100 mm) for the beginning, the middle and the end phase of the 5 s series of stimulation, and the respective averaged reflex size was calculated. The reflex size increased at stimulus frequencies 10 Hz × 0.8RT and 20 Hz × 0.8RT as compared with 5 Hz × 0.8RT (SNK, P<0.05), and by an increase in current intensity from 0.6RT to 0.8RT (SNK, P<0.05). Pain intensity increased with the increase in the current intensity from 0.6RT to 0.8RT (SNK, P<0.05). Profound activation of inhibition following electrocutaneous pain stimuli was demonstrated by reduction in pain intensity and reflex size during the last second as compared with the first second at 0.6RT current intensity (SNK, P<0.05). The pain intensity peaked between 5 and 10 Hz (P<0.05) and was reduced at 20 Hz for current intensities at 0.8RT (P<0.05). This study provides evidence for both frequency dependent central integration of the repetitive electrocutaneous stimuli and activation of a pain inhibitory system by psychophysical and electrophysiological means, demonstrating the delicate balance between neuronal facilitation and inhibition in the human pain system.