Diffuse analgesic effects of unilateral repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers

We investigated the analgesic effects of unilateral repetitive transcranial magnetic stimulation (rTMS) of the motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) in two models of experimental pain in healthy volunteers. Two studies were carried out in parallel in two groups of 26 paid healthy volunteers. The effects of active or sham rTMS (frequency, 10 Hz; intensity, 80% resting motor threshold) applied to the right M1 or DLPFC were compared in a double-blind randomized cross-over design. In the first series of experiments, we analyzed the effects of rTMS on thermal (heat and cold) detection and pain thresholds measured on both hands and the left foot, by standardized quantitative sensory testing methods. In the second series of experiments, we measured the effects of M1 or DLPFC rTMS on the threshold and recruitment curves of the RIII nociceptive reflex evoked by ipsilateral electrical stimulation of the sural nerve and recorded on the biceps femoris of both lower limbs. In both studies, measurements were taken before and up to 60 min after the end of rTMS. Active rTMS of both M1 and DLPFC significantly increased the thermal pain thresholds, measured for both hands and the left foot, this effect being most marked for cold pain. These effects, which lasted at least 1 h after rTMS, were selective because they were not associated with changes in non-painful thermal sensations. By contrast, the second study showed that rTMS of M1 or DLPFC had no significant effect on the threshold or recruitment curve of the nociceptive flexion RIII reflex. Our findings demonstrate that unilateral rTMS of M1 or DLPFC induces diffuse and selective analgesic effects in healthy volunteers. The lack of effect on the RIII reflex suggests that such analgesic effects may not depend on the activation of descending inhibitory systems.