High-frequency stimulation-induced secondary hyperalgesia shifts temporal order judgment and increases precuneus...

Pain can influence attention and other higher-order cognitive processes. In experimental settings, acute pain has been linked to attentional prioritization of the painful body region. However, conventional experimental pain models often rely on brief, phasic nociceptive stimuli and are therefore less suited to examining spatial attention during a sustained, experimentally induced sensitized state. In this study, we examined whether high-frequency stimulation (HFS)-induced secondary hyperalgesia, as a model of acute experimental sensitization, was associated with changes in temporal order judgment (TOJ) and resting-state EEG-derived measures in healthy adults. Sixteen healthy adults (mean age, 28.5 years; seven women) underwent HFS of the forearm to induce secondary hyperalgesia. Spatial attention was assessed using a TOJ task, and resting-state EEG data were analyzed using source-level graph-theoretical measures. HFS increased pinprick pain sensitivity in the surrounding skin adjacent to the stimulation site. TOJ performance showed a significant shift in the point of subjective simultaneity (PSS) toward the HFS-treated side, indicating an attentional bias independent of subjective pain intensity. EEG analysis revealed a significant increase in nodal degree in the bilateral precuneus in the theta band, and this change was positively correlated with the PSS shift (ρ = 0.53, p = 0.036). These findings suggest that both behavioral attentional bias and short-term changes in resting-state EEG-derived measures can accompany acute experimentally induced sensitization. The present results should be interpreted within the scope of the HFS model as reflecting short-term modulation during an acute sensitized state rather than chronic pain-like reorganization.