Long-term facilitation of nociceptive withdrawal reflexes following low-frequency conditioning electrical stimulation: A new model for central sensitization in humans

Central sensitization is believed to be one of the key mechanisms behind chronic pain conditions, and several models have been developed in order to characterize this phenomenon in humans. One of these models relies on conditioning electrical stimulation to elicit long-lasting effects on the nociceptive system. The aim of this study was to evaluate these effects using an objective electrophysiological measurement, the nociceptive withdrawal reflex (NWR). Long-term changes in spinal nociception after high- and low-frequency conditioning electrical stimulation were assessed in 13 healthy volunteers. Perceptual intensity ratings to mechanical stimuli and blood flow variations were assessed in the conditioned area (dorsum of the foot) and surroundings. To evaluate the excitability of the nociceptive system, the NWR was elicited within the same innervation area (superficial peroneal nerve) at graded stimulation intensities and recorded in the hamstrings. Following low-frequency stimulation, an intensity-independent long-lasting facilitation of the NWR was observed, with a significant increase in the reflex size (average of 31 ± 4%, p < 0.001) and in the number of reflexes (average increase of 22 ± 10%, p < 0.01), accompanied by a significant increase in the blood flow (average increase of 40 ± 10%, p < 0.001). These findings suggest that activity-dependent central sensitization can be elicited using conditioning electrical stimulation with a stimulation frequency that lies within the physiological firing range of primary afferents, and that it can be objectively assessed in humans using the NWR.