Chowdhury Nahian S, Millard Samantha K, de Martino Enrico, Larsen Dennis Boye, Seminowicz David A, Schabrun Siobhan M, de Andrade Daniel Ciampi, Graven-Nielsen Thomas
Center for Neuroplasticity and Pain (CNAP), Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
Center for Pain IMPACT, Neuroscience Research Australia, Sydney, New South Wales, Australia.
Pain. 2025 Jun 1;166(6):1314-1327. doi: 10.1097/j.pain.0000000000003488. Epub 2024 Dec 11.
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.
高频重复经颅磁刺激（rTMS）作用于后上岛叶（PSI）可能产生镇痛效果。然而，PSI-rTMS镇痛期间皮质活动的变化仍知之甚少。本研究旨在确定辣椒素诱导的持续性疼痛和皮质抑制（使用TMS-脑电图进行评估）是否受PSI-rTMS调节。20名健康志愿者（10名女性）参加了2次实验，随机接受主动或假rTMS治疗。通过将辣椒素涂抹在前臂90分钟来诱导实验性疼痛，每5分钟收集一次疼痛评分。在涂抹辣椒素约50分钟后进行左侧PSI-rTMS（10Hz，每串100个脉冲，共15串）。在基线、rTMS前辣椒素疼痛期间以及rTMS后评估经颅磁刺激诱发电位（TEP）和热敏感性。主动rTMS后发现疼痛评分降低和热痛阈值升高的贝叶斯证据，假rTMS后无变化。疼痛（主动rTMS前）导致额叶负峰约45毫秒（N45）TEP相对于基线增加。主动rTMS后，N45峰降低至基线水平。相比之下，假rTMS后，N45峰相对于基线增加。我们还发现，主动rTMS与假rTMS相比，疼痛数字评分量表得分的降低与N45峰的降低相关且部分由其介导。这些发现提供了PSI-rTMS镇痛作用的证据，并表明TEP N45峰是疼痛和镇痛的潜在标志物和介导因素。本研究表明，针对后上岛叶的高频rTMS可减轻辣椒素诱导的疼痛并改变皮质活动，N45 TMS诱发电位峰的变化介导了镇痛作用。
