Modulation of Electrical Brain Responses by Nociceptive Stimulus Properties

The development of treatments for chronic pain requires a more profound understanding of the physiological and psychological aspects of chronic pain. Several types of chronic pain are linked to increased sensitivity of the central nervous system. Therefore, it is important to study the underlying mechanisms of this increased sensitivity. However, one major obstacle is the lack of an objective measure of peripheral and central sensitivity. Tracking psychophysical thresholds of nociceptive specific electrocutaneous stimuli can facilitate the investigation of the underlying mechanisms of sensitization. Recently, a subjective method was developed for tracking multiple psychophysical thresholds over time, referred to as multiple threshold tracking (MTT), which has been shown sensitive to central changes in nociception. An objective measure of nociception related activity in the central nervous system is the electroencephalographic (EEG) signal. Multiple-trial averages of this signal, referred to as evoked potentials (EPs), have been shown to reflect nociceptive sensitivity to changes in stimulus parameters such as the number of pulses or number of trials. Since MTT has been shown to be effective in measuring the effect of stimulus parameters on stimulus detection, while the EP has been shown to reflect neurophysiological activity related to stimulus processing, a combination of both techniques might provide insight into the relation between neurophysiological activity and nociceptive stimuli. Both measures are subject to a large amount of noise as well as variation between measurements, leading to a poor signal-to-noise ratio (SNR). Doll et al. have shown that a generalized linear mixed model (GLMM) can be used to account for this variation in MTT measurements, while computing an estimate of the within-subject psychophysical function that is robust to noise. A similar mixed-regression analysis of the EPs during MTT is expected to successfully account for between-subject variations, and provide objective measures of peripheral and central sensitization.

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Each subject will participate one single time in the experiment. The duration of the main experiment is approximately 50 minutes.

The participants will be asked to come to the Human Physiology Lab of the BSS Group at the University of Twente for one session. First, the participant is familiarized with the stimuli by stepwise application of increasing stimuli until stimulus detection. During the experiment, the participant will receive randomized stimuli around the detection threshold according to the multiple threshold tracking paradigm. Several types of nociceptive stimuli will be applied, while the subject’s response (detected or not detected) and the stimulus related EEG epochs will be measured.