A reappraisal of pain-paired associative stimulation suggesting motor inhibition at spinal level

Abstract

Paired associative stimulation (PAS) can modulate motor excitability and consists of delivering repeated pairs of peripheral sensory stimulation combined with transcranial magnetic stimulation (TMS) over the contralateral motor cortex. Our objective was to evaluate the effect of a PAS protocol using a painful stimulation. Ten healthy volunteers underwent pain-PAS protocol consisting of 90 pairs of nociceptive stimulus over the right hand followed by an image-guided navigated TMS of the contralateral motor cortex, delivered at 0.1Hz over 15minutes. Four distinct inter-stimuli intervals (ISI) were assessed: -40ms, +10ms, +30ms and +50ms with respect to the individual pain-related evoked potential (N2 latency). The impact of pain-PAS was assessed by measuring motor evoked potentials (MEPs) amplitudes before and up to 30minutes after the pain-PAS procedure. For the "N2 latency -40ms" ISI condition, a significant decrease of MEP amplitude was observed in the immediate post-pain-PAS period. For longer ISIs, no significant changes were observed. A motor inhibition effect was produced by repetitive pairs of painful peripheral stimulation and TMS pulse delivered to the motor cortex before the afferent volley reaches the somatosensory cortex. This short ISI falls into a period of time corresponding to the cutaneous silent period, suggesting that the motor inhibition effect produced by pain-PAS could occur at spinal level. The repeated interaction of the nociceptive afferent input and the descending motor corticospinal volley could lead to reduced excitability of homonymous spinal motoneurons.