Psychophysical and Neurophysiological Correlates of Nociceptive Paired-Pulse Facilitation

Activity: Talk or presentationOral presentation


Introduction: When peripheral nociceptive nerve fibers are stimulated by two consecutive pulses instead of one, the subjective detection probability increases much more than would be expected based on probability summation [1]. The additional increase in detection probability is most likely related to short-term synaptic facilitation. As this facilitation might occur at synaptic connection in the spinal cord, it can be expected that this facilitation can also be observed by an altered neurophysiological response in the EEG. We investigate if facilitation of the detection probability can be reproduced in a new experiment where we simultaneously measure detection probability and EEG, and assess if changes in detection probability are associated with changes of neurophysiological activity measured by EEG. Methods: Single and double-pulse stimuli are applied to 30 healthy subjects via intra-epidermal electrocutaneous stimulation. Nociceptive detection thresholds are tracked by randomized application of 450 stimuli around the detection threshold according to the adaptive probing paradigm [2], while simultaneously recording a 128-channel EEG. The detection probability of single-pulse and double-pulse stimuli are computed using logistic regression with respect to the responses. Neurophysiological facilitation is measured by subtracting the contribution of the first pulse from the contribution of the second pulse to the EEG response. Both contributions are computed using linear mixed regression. The Medical Ethics Committee Twente approved all experimental procedures. Results: The first and the second pulse of a nociceptive stimulus around the detection threshold significantly increase the detection probability and the EEG response. However, the second pulse has a larger effect on both measures. The detection probability increases much more than one would expect based on probability summation and there is a positive difference between the second-pulse and the first-pulse contribution to the EEG with a central topography at 420ms. Conclusion: Nociceptive paired-pulse facilitation can be observed by an increase in subjective detection probability and a larger contribution of the second pulse of a stimulus to the EEG response. Both types of observations might contribute to the study of medication and pathologies potentially influencing synaptic facilitation. REFERENCES 1. Doll, R.J., Maten, A. C., Spaan, S. P., Veltink, P. H., & Buitenweg, J. R., Effect of temporal stimulus properties on the nociceptive detection probability using intra-epidermal electrical stimulation. Experimental brain research, 234(1), 2016: p. 219-227. 2. Doll, R.J., Buitenweg, J. R., Meijer, H. G., & Veltink, P. H., Tracking of nociceptive thresholds using adaptive psychophysical methods. Behavior research methods, 46(1), 2014: p. 55-66.
Period25 Jan 2019
Event title7th Dutch Bio-Medical Engineering Conference, BME 2019
Event typeConference
Conference number7
LocationEgmond aan zee, NetherlandsShow on map
Degree of RecognitionNational


  • Evoked Potential
  • Nociceptive Processing
  • Paired-pulse Facilitation
  • Linear Mixed Regression