Whether, how, and which cognitive factors modulate the development of secondary hypersensitivity/hyperalgesia following central sensitization is not fully understood. Here we tested, in three subsequent experiments, whether being engaged in non-pain related cognitive demanding tasks: i) lessens the amount of hypersensitivity developed after an experimental procedure sensitizing nociceptive pathways; ii) modulates cortical responses to somatosensory stimuli (measured by electroencephalography, EEG). In the first experiment we validated a novel model in humans using low frequency stimulation (LFS) of the skin and demonstrated that it was able to successfully induce hypersensitivity to mechanical pinprick stimuli in the area surrounding the sensitized site. In the second and third experiments we engaged participants in tasks of increasing difficulty (the Eriksen Flanker Task in experiment 2, and a modified N-back task in experiment 3). We observed that hypersensitivity to mechanical stimuli still developed in experiment 2, i.e. the pinprick stimuli applied on the sensitized arm were perceived as more intense after LFS. In contrast, no statistically significant enhancement of mechanical hypersensitivity was observed in experiment 3, indicating that, at the group level, being engaged in a difficult N-back task may interfere with the development of mechanical hypersensitivity. Contrary to previous studies, which have used different methods to induce sensitization, we did not observe any increase in the cortical response to somatosensory stimuli applied on the sensitized arm. We conclude that i) the development of pinprick hypersensitivity is modulated by the concomitant execution of a difficult N-back task, and ii) the enhancement of cortical responses to somatosensory stimuli is related to the method used to induce central sensitization.

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