Modulation of Electrical Brain Responses by Nociceptive Stimulus Properties and Stimulus Detection: an Exploratory Study

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 [1]. 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 [2].
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 [3]. 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 [4, 5] or number of trials [6]. 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. [3]
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.

The primary objective of this study is to describe the quality and content of
electrical brain responses of pain free subjects to electrocutaneous stimuli
during multiple threshold tracking, by determining the signal-to-noise ratio of
averaged responses and by exploration of the use of generalized linear mixed
models to explain the variability in these responses.

Mono-center, cross-sectional study.

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. All participants will be compensated for their
participation. The participants will obtain no direct personal benefit.