Simultaneous tracking of psychophysical detection thresholds and evoked potentials to study nociceptive processing

Abstract

Measuring altered nociceptive processing involved in chronic pain is difficult due to a lack of objective methods. Potential methods to characterize human nociceptive processing involve measuring neurophysiological activity and psychophysical responses to well-defined stimuli. To reliably measure neurophysiological activity in response to nociceptive stimulation using EEG, synchronized activation of nerve fibers and a large number of stimuli are required. On the other hand, to reliably measure psychophysical detection thresholds, selection of stimulus amplitudes around the detection threshold and many stimulusresponse pairs are required. Combining the two techniques helps in quantifying the properties of nociceptive processing related to detected and non-detected stimuli around the detection threshold. The two techniques were combined in an experiment including 20 healthy participants to study the effect of intra-epidermal electrical stimulus properties (i.e. amplitude, single-or double-pulse and trial number) on the detection thresholds and vertex potentials. Generalized mixed regression and linear mixed regression were used to quantify the psychophysical detection probability and neurophysiological EEG responses, respectively. It was shown that the detection probability is significantly modulated by the stimulus amplitude, trial number, and the interaction between stimulus type and amplitude. Furthermore, EEG responses were significantly modulated by stimulus detection and trial number. Hence, we successfully demonstrated the possibility to simultaneously obtain information on psychophysical and neurophysiological properties of nociceptive processing. These results warrant further investigation of the potential of this method to observe altered nociceptive processing.

Observation of Nociceptive Processing: Effect of Intra-Epidermal Electric Stimulus Properties on Detection Probability and Evoked Potentials

“…3. In earlier studies, this effect was also found significant, but had a larger effect size (Doll et al 2016a, b;van den Berg et al 2020). Altered habituation appears to play an important role in several types of chronic pain syndromes, and is therefore an important phenomenon to observe when assessing nociceptive processing (Agostinho et al 2009;Rodriguez-Raecke et al 2014;Valeriani et al 2003).…”

“…Measuring this habituating behavior can be used to assess altered nociceptive processing. A decreased habituation of P2 amplitude over time or over the amount of repeated stimuli has been related to chronic pain in earlier literature in patients with migraine (Valeriani et al 2003), chronic low back pain (Vossen et al 2015) and fibromyalgia (de Tommaso et al 2011).…”

“…This technique has been shown to preferentially activate nociceptive afferents when applied at less than two times the detection threshold (Mouraux et al 2010 ; Poulsen et al 2020 ). Recently, we developed a method to concentrate stimulation around this (drifting) detection threshold, and measure stimulus–response pairs and evoked potentials in response to these nociceptive stimuli (van den Berg et al 2020 ).…”

“…After a technical pilot study (van den Berg et al 2020 ), we designed a new study with the combined measurement of detection thresholds and evoked potentials to accurately quantify the effect of intra-epidermal stimulus properties, i.e. number of pulses and inter-pulse interval, on both outcome measures in healthy individuals.…”

Use-Dependent Plasticity Enhances Nociceptive and Non-Nociceptive Somatosensory Cortical Responses in Healthy Individuals

“…Previous electrophysiological studies exploring use-dependent plasticity are typically based on a total sample size between 15-44 participants (Kühnis et al, 2014; Pantev et al, 2001; Vuust et al, 2008). Moreover, studies using the same intra-epidermal electrical stimulation to elicit nociceptive electrophysiological responses as in the current study report total sample sizes of 5-20 participants (Biurrun Manresa et al, 2018; Mouraux et al, 2014, 2010; van den Berg et al, 2020). To ensure a robust estimate of our neurophysiological effect, a total sample of 40 participants was recruited for the current study.…”