931) (see  Fig. 3). This study is, to our knowledge, the first to use the combination of selective stimulation of nociceptive afferents, balanced psychometric tasks assessing different aspects of pain perception, and single-pulse TMS over multiple cortical areas. We applied single-pulse TMS to cortical areas S1 or S2, or a non-active control site, shortly after laser stimulation. Participants judged the stimulus intensity or location. Our results showed that

TMS over S2 disrupted Lapatinib perception of pain intensity, but not of pain location. TMS reduced sensitivity to stimulation intensity, without producing any systematic bias in perceived pain levels. These results are consistent with TMS over S2 disrupting the information-processing that underlies the perception of pain intensity. TMS over S1 had no significant effects on perception of either pain intensity or pain location. We conclude that Selleckchem Rapamycin S2 causally contributes to the ability to discriminate the intensity of a painful stimulus. Several previous studies had suggested that S2 might code pain intensity (e.g., Bornhövd et al., 2002; Coghill et al., 1999; Frot et al., 2007; Iannetti et al., 2005; Timmermann et al., 2001; Valmunen et al., 2009). Our finding provides clear causal evidence for a role of S2 in the ability to discriminate the intensity of a painful stimulus using nociceptive-selective stimulation and a well-characterised

psychometric task. Further, signal-detection analyses showed that TMS over S2 affected judgements of pain intensity by abolishing perceptual sensitivity to stimulus intensity, and not by simply masking pain, or shifting pain levels up or down. Participants’ sensitivity to actual stimulus intensity was reduced i.e.,

the precision of their pain perception. There was no significant bias in pain judgement, either analgesic or hyperalgesic. Our finding confirms previous observations from Valmunen Acetophenone et al. (2009) who reported that rTMS over S2 affected heat pain judgements. Specifically, they found that S2 stimulation both impaired judgements of pain intensity, and reduced perceived pain intensity. We replicated the reduced sensitivity, but not the hypoalgesic bias. Our results also extend their finding, in two ways. First, our result conclusively links S2 to nociceptive processing. Valmunen et al. delivered contact-heat somatosensory stimuli, which inevitably coactivate nociceptive and tactile systems. Given that nociceptive and tactile codes interact at several levels in the nervous system (Melzack and Wall, 1965), the methods used by Valmunen et al. cannot exclude the possibility of indirect effects on pain, as a result of interactions with touch. In contrast, the nociceptive stimulation used in the present study was entirely specific. Second, we show that a single-pulse TMS applied to coincide with the onset of the LEP component is able to disrupt pain coding.