Background & Aims
The high frequency stimulation (HFS) model is associated with the gradual development of homotopic and heterotopic pain sensitivity [1]. These temporal changes in sensitivity and the associated cortical responses can be assessed using psychophysical pain ratings alongside electroencephalography (EEG) [2]. However, the test re-test reliability of this combined multimodal approach to assessing the gradual HFS-induced changes in central nociceptive pathways is poorly understood. Therefore, this study assessed the test-retest reliability of changes in perceived pain sensitivity to acute mechanical and electrical nociceptive stimulation in concert with EEG evoked responses at four timepoints following HFS.
Methods
17 healthy participants (9 male, expected final sample N = 30) attended 2 sessions a week apart. In both sessions, participants underwent HFS conditioning over the volar surface of the forearm. Numerical pain ratings (NRS) in response to mechanical and single pulse electrical stimulation were then collected in heterotopic and homotopic zones on both forearms at baseline and at 5, 20, 35 and 50 minutes post HFS. EEG data were also collected continuously with triggers time-locked to nociceptive stimuli. Change from baseline NRS z-scores were compared via two-way repeated measures analysis of variance (ANOVA). Test re-test reliability was assessed using single-measure, absolute agreement, two-way mixed-effects model intraclass correlation coefficients (ICC3,1). Prospectively, relationships between EEG (evoked potentials; spectra; source localisation), conditioned pain modulation and psychometric data with NRS results will be calculated.
Results
For the MPS test arm, there was a significant effect of time (F=3.18, p=0.02) but no effect of session (F=0.21, p=0.65). ICCs calculated for changes in MPS demonstrated moderate-to-good test-retest reliability for all timepoints at 5, 20, 35 and 50 minutes (ICC= 0.62, 0.55, 0.47, 0.66 respectively), with the greatest increase in MPS occurring alongside the highest ICC value at 50 minutes post HFS for both sessions. For the MPS control arm, there was no significant effect of time (F=1.45, p=0.24), but there was significant effect of session (F=1.41, p = 0.04) and all timepoints demonstrated good-to-excellent ICC (ICC=0.69, 0.60, 0.74, 0.65). For electrical stimulation, only the control arm had a significant effect of time (F=0.31, p = 0.03). Both the test and control arms showed no effect of session (F=0.01, p=0.92, and F=0.30. p=0.59), and moderate-to-excellent ICC across all timepoints (test: ICC=0.78, 0.84, 0.78, 0.49; control: ICC=0.67, 0.77, 0.45, 0.61).
Conclusions
Our current interim findings demonstrated moderate-to-good test-retest reliability for both pinprick and electrically evoked psychophysical responses across test and control sites. The test arm MPS also showed significant evidence of the induction of secondary hyperalgesia post-HFS with the most robust ICC and highest MPS occurring in tandem at 50 minutes. Further analysis will utilise the full multimodal dataset being collected as part of this larger study to compare the reliability of psychophysical measures with nociceptive evoked potentials and investigate their relationships with EEG resting-state spectra and source generators, conditioned pain modulation, and psychometric questionnaire data.
References
[1] Fawsitt-Jones H, Vollert J, O’Daly O, Williams SCR, McMahon SB, Howard MA, Hughes SW (2023). Reliability of quantitative sensory testing in the assessment of somatosensory function after high-frequency stimulation–induced sensitisation of central nociceptive pathways. Pain, 1097(10).
[2] Broeke, E. N. V. den, Urd, M., Mouraux, A., Manresa, J. A. B., & Torta, D. M. E. (2021). High-frequency electrical stimulation of cutaneous nociceptors differentially affects pain perception elicited by homotopic and heterotopic electrical stimuli. Journal of Neurophysiology, 126(4), 1038–1044.