661: Sensory Gain Increase in Secondary Hyperalgesia beyond Attentional Effects

Topic: Experimental (Non-clinical) Human Studies
Subtopic: Non -specific to any diagnosis, Electrophysiology/Clinical neurophysiology (e.g. microneurography, EEG, MEG, OPMs, TMS), Pain models (e.g. saline injection, capsaicin, UVB, HFS, incision, exercise, itch), Quantitative Sensory testing (static and dynamic, e.g., HPT, PPT, CPM, TSP, offset analgesia)

Background and Aims: Experimental models of secondary hyperalgesia in humans suggest that nociceptive sensitization modulates the processing of non-nociceptive stimuli [1, 2]. After high-frequency electrical stimulation (HFS), vibrotactile stimuli delivered to the hyperalgesic area elicit enhanced cortical responses, reflected in increased N140 event-related potentials [1]. However, N140 amplitude is also modulated by spatial attention [3], a factor not controlled in previous studies. Consequently, the reported increase may partly reflect attentional allocation to the stimulated arm rather than sensitization alone. Therefore, the present study aimed to replicate these findings [1] while explicitly controlling attentional allocation to vibrotactile stimuli presented after HFS.

Methods: Forty participants (21 women) completed four blocks of a somatosensory oddball task before and 20 minutes after HFS was applied to one forearm. In each block, vibrotactile stimuli were delivered to one forearm, ensuring attention was directed to one arm at a time, and participants responded to infrequent deviants among frequent standards. Primary outcomes were N140 amplitude at Cz elicited by vibrotactile stimuli, reaction times, accuracy, and intensity ratings for mechanical pinprick (assessing secondary hyperalgesia) and vibrotactile stimuli. Preregistered analyses used linear mixed models to test Side (HFS vs. Control) × Time interactions, while exploratory analyses examined habituation across blocks.

Results: HFS successfully induced mechanical hypersensitivity, as reflected by increased mechanical pinprick ratings in the sensitized arm relative to both baseline and the control arm (p<.001). Vibrotactile intensity ratings also increased in the sensitized arm compared with baseline and the control condition (p< .001). Reaction times showed no significant Side × Time interaction (p=.54). In contrast, hit-rate accuracy demonstrated a trend-level interaction higher for the sensitized arm (p=.06). N140 amplitudes elicited by vibrotactile stimuli increased selectively in the sensitized arm following HFS (p=.026) relative to baseline and control. Habituation across blocks was observed over Time, independently of Side (p<.001).

Conclusions: We successfully replicated N140 enhancement elicited by vibrotactile stimuli in the area of mechanical hypersensitivity [1]. The dissociation between amplified cortical responses and unchanged reaction times suggests that attentional allocation is not the primary mediator. However, the trend-level increase in accuracy toward the sensitized arm does not allow a complete exclusion of attentional contributions and supports a more complex model of cortical modulation. These findings demonstrate that HFS-induced sensitization reliably modulates vibrotactile processing at cortical levels, and point towards a sensory amplification pattern that is, nonetheless, not fully independent of attentional effects.

References: 1. van den Broeke, E. N., & Mouraux, A. (2014). High-frequency electrical stimulation of the human skin induces heterotopical mechanical hyperalgesia, heat hyperalgesia, and enhanced responses to nonnociceptive vibrotactile input. Journal of neurophysiology, 111(8), 1564–1573.
2. Torta, D. M. E., Van Den Broeke, E. N., Filbrich, L., Jacob, B., Lambert, J., & Mouraux, A. (2017). Intense pain influences the cortical processing of visual stimuli projected onto the sensitized skin. Pain, 158(4), 691–697.
3. Eimer, M., & Forster, B. (2003). Modulations of early somatosensory ERP components by transient and sustained spatial attention. Experimental brain research, 151(1), 24–31.

Presenting Author: Diana Torta
Submitting Author: Aurelia Scarpa

Senior Author: Diana Torta

IASP 2026 Global Year theme of Neuropathic Pain: No

• Diana Torta: Professor - KU Leuven