This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

related potentials (ERPs) elicited by transient nociceptive stimuli in humans are largely sensitive to bottom-up novelty induced, for example, by changes in stimulus attributes (e.g., modality or spatial location) within a stream of repeated stimuli. Here we aimed 1) to test the contribution of a selective change of the intensity of a repeated stimulus in determining the magnitude of nociceptive ERPs, and 2) to dissect the effect of this change of intensity in terms of "novelty" and "saliency" (an increase of stimulus intensity is more salient than a decrease of stimulus intensity). Nociceptive ERPs were elicited by trains of three consecutive laser stimuli (S1-S2-S3) delivered to the hand dorsum at a constant 1-s interstimulus interval. Three, equally spaced intensities were used: low (L), medium (M), and high (H). While the intensities of S1 and S2 were always identical (L, M, or H), the intensity of S3 was either identical (e.g., HHH) or different (e.g., MMH) from the intensity of S1 and S2. Introducing a selective change in stimulus intensity elicited significantly larger N1 and N2 waves of the S3-ERP but only when the change consisted in an increase in stimulus intensity. This observation indicates that nociceptive ERPs do not simply reflect processes involved in the detection of novelty but, instead, are mainly determined by stimulus saliency. habituation; pain; electroencephalography; stimulus intensity BRIEF INFRARED LASER HEAT pulses selectively activate A␦ and C fiber skin nociceptors in the superficial skin layers (Bromm and Treede 1984). Such stimuli elicit transient event-related potentials [laser-evoked potentials (LEPs)], related to the activation of A␦ nociceptors. The largest LEP wave is a negative-positive complex maximal at the scalp vertex (N2-P2). This complex is preceded by a smaller negative wave (N1) maximal over the central-temporal region contralateral to the stimulated hand (Bromm and Treede 1984;Hu et al. 2010;Valentini et al. 2012). These waves reflect a combination of cortical activities originating from primary and secondary somatosensory cortices, the insula, and the anterior cingulate cortex (Garcia-Larrea et al. 2003;Valentini et al. 2012).Although widely used to investigate the function of nociceptive pathways in health and disease (Haanpaa et al. 2011), the physiological meaning of LEPs is still debated. Indeed, recent experimental evidence indicates that LEPs may reflect stimulus-triggered brain processes largely unspecific for nociception. Indeed, similar brain responses can be elicited by nonnociceptive sensory stimuli that are never perceived as painful, provided that they are salient (Legrain et al. 2011;Mouraux and Iannetti 2009). Furthermore, the well-known positive correlation between the intensity of perceived pain and the magnitude of LEPs can be disrupted in several experimental conditions, such as stimulus repetition at a short and constant interval Treede et al. 2003;Wang et al. 2010).Finally, there is a large amount of evidence that the main LEP waves can be modu...

21The event-related brain potentials (ERPs) elicited by nociceptive stimuli are largely influenced by 22 vigilance, emotions, alertness and attention. Studies that have specifically investigated the effects of 23 cognition on the nociceptive ERPs support the idea that most of the components of these ERPs can 24 be regarded as the neurophysiological indexes of the processes underlying the detection and the 25 orientation of attention toward the eliciting stimulus. Such detection is determined by the salience of 26 the stimulus that makes it pop out from the environmental context (bottom-up capture of attention) 27and by its relevance according to the subject's goals and motivation (top-down attentional control). 28The fact that nociceptive ERPs are largely influenced by information from other sensory modalities 29 such as vision and proprioception, as well as from motor preparation, suggests that these ERPs 30 reflect a cortical system involved in the detection of potentially meaningful stimuli for the body, with 31 the purpose to respond adequately to potential threats. In such a theoretical framework, pain is seen 32 que par la préparation motrice suggèrent que ces PE reflètent un système cortical impliqué dans la 55 détection des stimuli potentiellement significatifs pour l'organisme dans le but de répondre 56 adéquatement aux menaces éventuelles. Dans un tel cadre théorique, la douleur est considérée 57 comme un épiphénomène des processus d'alerte, intégré dans des représentations multimodales et 58 multi-référentielles du corps dont le but est de guider la réalisation des comportements de défense. 59Les données présentées dans cet article soulignent que les PE obtenus en réponses à des 60 stimulations sélectives des nocicepteurs peuvent représenter l'activité des mécanismes de contrôle 61 du gain attentionnel permettant de coordonner de façon cohérente la perception d'événements 62 sensoriels saillants et la sélection de la réponse. 63 64