Posterior-superior insula repetitive transcranial magnetic stimulation reduces experimental tonic pain and pain-related cortical inhibition in humans

Nahian S Chowdhury; Samantha K Millard; Enrico de Martino; Dennis Boye Larsen; David A Seminowicz; Siobhan M Schabrun; Daniel Ciampi de Andrade; Thomas Graven-Nielsen

doi:10.1097/j.pain.0000000000003488

Posterior-superior insula repetitive transcranial magnetic stimulation reduces experimental tonic pain and pain-related cortical inhibition in humans

Pain. 2024 Dec 11. doi: 10.1097/j.pain.0000000000003488. Online ahead of print.

Authors

Nahian S Chowdhury^{1

2

3}, Samantha K Millard¹, Enrico de Martino¹, Dennis Boye Larsen¹, David A Seminowicz⁴, Siobhan M Schabrun^{5

6}, Daniel Ciampi de Andrade¹, Thomas Graven-Nielsen¹

Affiliations

¹ Center for Neuroplasticity and Pain (CNAP), Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
² Center for Pain IMPACT, Neuroscience Research Australia, Sydney, New South Wales, Australia.
³ University of New South Wales, Sydney, New South Wales, Australia.
⁴ Department of Medical Biophysics, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Canada.
⁵ The Gray Centre for Mobility and Activity, Parkwood Institute, London, Canada.
⁶ School of Physical Therapy, University of Western Ontario, London, Canada.

PMID: 39679661
DOI: 10.1097/j.pain.0000000000003488

Abstract

High frequency repetitive transcranial magnetic stimulation (rTMS) to the posterior-superior insula (PSI) may produce analgesic effects. However, the alterations in cortical activity during PSI-rTMS analgesia remain poorly understood. The present study aimed to determine whether tonic capsaicin-induced pain and cortical inhibition (indexed using TMS-electroencephalography) are modulated by PSI-rTMS. Twenty healthy volunteers (10 females) attended 2 sessions randomized to active or sham rTMS. Experimental pain was induced by capsaicin administered to the forearm for 90 minutes, with pain ratings collected every 5 minutes. Left PSI-rTMS was delivered (10 Hz, 100 pulses per train, 15 trains) ∼50 minutes postcapsaicin administration. Transcranial magnetic stimulation-evoked potentials (TEPs) and thermal sensitivity were assessed at baseline, during capsaicin pain prior to rTMS and after rTMS. Bayesian evidence of reduced pain scores and increased heat pain thresholds were found after active rTMS, with no changes occurring after sham rTMS. Pain (prior to active rTMS) led to an increase in the frontal negative peak ∼45 ms (N45) TEP relative to baseline. After active rTMS, there was a decrease in the N45 peak back to baseline levels. In contrast, after sham rTMS, the N45 peak was increased relative to baseline. We also found that the reduction in pain numerical rating scale scores after active vs sham rTMS was correlated with and partially mediated by decreases in the N45 peak. These findings provide evidence of the analgesic effects of PSI-rTMS and suggest that the TEP N45 peak is a potential marker and mediator of both pain and analgesia. This study demonstrates that high-frequency rTMS targeting the posterior-superior insula reduces capsaicin-induced pain and alters cortical activity, with changes in the N45 TMS-evoked potential peak mediating the analgesic effects.

Abstract

Grants and funding