The effect of prolonged elbow pain and rTMS on cortical inhibition: A TMS-EEG study

Recent studies using combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) have shown that pain leads to an increase in the N45 peak of the TMS-evoked potential (TEP), which is mediated by GABAergic inhibition. Conversely, 10Hz repetitive TMS (10Hz-rTMS), which provides pain relief, reduces the N45 peak. However, these studies used brief pain stimuli (lasting minutes), limiting their clinical relevance. The present study determined the effect of pain and 10Hz-rTMS on the N45 peak in a prolonged pain model (lasting several days) induced by nerve growth factor (NGF) injection to the elbow muscle.

Experiment 1 : TEPs were measured in 22 healthy participants on Day 0 (pre-NGF), Day 2 (peak pain), and Day 7 (pain resolution). Experiment 2 : We examined the effect of 5 days of active (n=16) or sham (n=16) rTMS to the left primary motor cortex (M1) on the N45 peak during prolonged NGF-induced pain, with TEPs measured on Day 0 and Day 4 (post-rTMS).

Experiment 1: While no overall change in the N45 peak was seen, a correlation emerged between higher pain severity on Day 2 and a larger increase in the N45 peak. Experiment 2 : Active rTMS reduced the N45 peak on Day 4 vs. Day 0, with no effect in the sham group.

Our findings suggest that (i) higher pain severity correlates with an increase in the N45 peak, and (ii) rTMS decreases cortical inhibition in a model of prolonged experimental pain. This study extends previous research by demonstrating a link between pain perception and cortical inhibition within a prolonged pain context.