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OBJECTIVE
We investigated the influence of paired-pulse transcranial magnetic stimulation (ppTMS) of the motor cortex (M1) on perception of noxious electrical stimuli. The nociceptive flexion reflex response was assessed to determine spinal effects.

METHODS
In the first experiment, the effect of ppTMS of M1 on perception of noxious stimulation of the sural nerve was assessed by varying the stimulus onset asynchronies (SOAs) and the order of the stimulations (-400, -75, -25, 25, 125, 400 ms and control ppTMS, negative sign: ppTMS precedes the noxious stimulation). Effects of a preceding ppTMS on the RII and the RIII response of the nociceptive flexion reflex were investigated for SOAs of -400 and -75 ms. The effects of ppTMS of M1 and of the occipital cortex (Oz) on noxious stimulation of the radial nerve were investigated in a second experiment. Visual analogue scales were used to assess pain intensity and unpleasantness.

RESULTS
The results revealed increased pain unpleasantness scores for SOAs of -75, -25, 25, and 400 ms and decreased pain intensity scores for a SOA of -400 ms, when the sural nerve and M1 were stimulated. An increase of the area of the RII response was found for a SOA of -75 ms. For stimulation of the radial nerve, ppTMS of Oz but not of M1 increased the perceived pain at a SOA of 25 ms.

DISCUSSION
The facilitatory component of ppTMS led to increased pain perception when applied during the cortical process of Adelta fiber-mediated input, whereas the subsequent inhibitory component may lead to the opposite effect on the subsequent noxious stimulation.