Background & Aims
Non-invasive brain stimulation, such as repetitive transcranial magnetic stimulation (rTMS), has emerged as a potential treatment for pain. The application of rTMS to specific cortical sites, such as the primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC), has been widely explored for pain relief [2-4]. A recent study showed that high frequency rTMS to the M1, but not DLPFC-rTMS, induced relief of peripheral neuropathic pain over 25?weeks with excellent safety profile [1]. However, the mechanisms underlying pain relief induced by M1-rTMS and DLPFC-rTMS remain unclear. This study, employing an experimentally-induced heat pain model and EEG techniques, aims to delineate the temporal courses of analgesic effects induced by M1-rTMS and DLPFC-rTMS, along with investigating the underlying neural mechanisms.
Methods
In a double-blinded, sham-controlled design, 120 healthy participants were recruited to undergo 10 Hz rTMS over the M1 or DLPFC, or sham stimulation. Pain-rating tasks were conducted before (T0), immediately after (T1), and 60 minutes after (T2) rTMS application to assess pain anticipation and perception. Noxious laser stimuli were applied to the dorsum of the right hand during the task, and participants verbally rated perceived pain on a 0–10 numerical rating scale. To investigate how rTMS at the M1 or DLPFC modulates pain perception, early (T1?T0) and late (T2?T0) effects of rTMS on laser-evoked potentials (LEPs) and subjective pain ratings were compared among the experimental groups. Exploratory analyses examined rTMS-induced modulation of the anticipation of upcoming pain, assessing early and late effects on the sensorimotor peak alpha frequency of anticipatory EEG signals, as well as effects on the temporal characteristics of EEG microstates (e.g., mean duration and occurrence).
Results
At the perceptual level, a more pronounced reduction in pain intensity was observed 60 minutes after DLPFC-rTMS compared to sham stimulation. At the neural level, a more pronounced reduction in P2 amplitudes immediately after M1-rTMS compared to sham stimulation. Moreover, N2 and P2 amplitudes attenuated more 60 minutes after DLPFC-rTMS compared to sham stimulation. Anticipatory EEG results indicated that M1-rTMS led to a more substantial elevation of sensorimotor peak alpha frequency compared with sham stimulation, persisting for 60 minutes after M1-rTMS application. Microstate analysis revealed an increase in the mean duration of microstate C 60 minutes after DLPFC-rTMS compared with M1-rTMS and sham stimulation. Correlation analysis indicated that M1-rTMS-induced elevation in peak alpha frequency was associated with its effect on attenuating N2 responses, while DLPFC-rTMS-induced increases in the duration of microstate C were associated with its effect on attenuating pain intensity.
Conclusions
This study demonstrates that rTMS over the M1 and DLPFC induces analgesic effects by attenuating laser-evoked responses, but with distinct temporal courses and neural mechanisms. High-frequency rTMS over the M1 exhibits an early analgesic effect on mitigating the affective component of LEPs, possibly linked to its impact on increasing sensorimotor peak alpha frequency during anticipation of upcoming pain. In contrast, high-frequency rTMS over the DLPFC manifests a late analgesic effect on mitigating laser-evoked pain intensity ratings and the N2-P2 complex, likely attributed to its impact on increasing the duration of microstate C, associated with subjective interoceptive–autonomic processing. Overall, these findings have the potential to guide the development of targeted and personalized non-invasive brain stimulation interventions for pain management, e.g., tailoring interventions based on individual pain processing characteristics.
References
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Presenting Author
Xiaoyun Li
Poster Authors
Xiaoyun Li
PhD
Shenzhen University
Lead Author
Topics
- Treatment/Management: Interventional Therapies – Neuromodulation