Evoked alpha oscillatory activity is suppressed by prolonged elbow pain and modulated by repetitive transcranial magnetic stimulation

Alpha-band oscillatory activity, assessed using electroencephalography (EEG), is among the most widely studied neurophysiological markers of pain. However, the literature has focused predominantly on resting-state measures, leaving unclear whether pain also alters evoked alpha-band dynamics, measured via cortical perturbation using transcranial magnetic stimulation (TMS). Here, we examined whether prolonged pain alters TMS-evoked alpha event-related spectral perturbation (ERSP) and intertrial coherence (ITC), reflecting cortical reactivity and phase consistency, and whether 10-Hz repetitive TMS (rTMS) modulates these responses. We performed a secondary analysis on 2 previous experiments, which used nerve growth factor (NGF) injection to induce prolonged elbow muscle pain. In experiment 1, participants underwent primary motor cortex (M1) TMS-EEG at baseline (day 0) pre-NGF injection and day 2 (peak pain) and day 7 (pain resolution) post-injection. In experiment 2, M1-TMS-EEG was assessed on day 0 before NGF injection and again on day 4 after injection, with active or sham 10-Hz rTMS delivered to M1 between these assessments. In experiment 1, M1 TMS-EEG showed reductions in alpha ERSP (P = 0.014) and alpha ITC (P = 0.041) from day 0 to day 2. In experiment 2, active rTMS produced a more positive pre-to-post change in alpha ERSP (P = 0.006) relative to sham but did not alter alpha ITC (P = 0.804). Our findings suggest that prolonged experimental pain is associated with diminished evoked alpha oscillatory activity, whereas high-frequency rTMS modulates this activity in the positive direction. These findings suggest that perturbation-evoked alpha metrics warrant further investigation as candidate biomarkers of pain state and response to neuromodulation.