Chowdhury Nahian S, Chang Wei-Ju, Cheng Donovan, Manivasagan Naveen, Seminowicz David A, Schabrun Siobhan M
Center for Pain IMPACT, Neuroscience Research Australia, Sydney, New South Wales, Australia.
University of New South Wales, Sydney, New South Wales, Australia.
Imaging Neurosci (Camb). 2025 May 22;3. doi: 10.1162/IMAG.a.7. eCollection 2025.
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), potentially linked to changes in GABAergic activity. Conversely, 10 Hz repetitive TMS (10 Hz-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 10 Hz-rTMS on the N45 peak in a prolonged pain model (lasting several days) induced by nerve growth factor (NGF) injection to the elbow muscle. In Experiment 1, TEPs were measured in 22 healthy participants on Day 0 (pre-NGF), Day 2 (peak pain), and Day 7 (pain recovery). In 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). Peak pain and muscle soreness was mild to moderate across experiments. In Experiment 1, there was no evidence for an increase in the N45 peak during prolonged pain. Exploratory analyses revealed evidence for a reduction in the N45 peak from Day 2 to 7, and a correlation between higher pain severity on Day 2 and a larger increase in the N45 peak. In Experiment 2, active rTMS reduced the N45 peak on Day 4 versus Day 0, with no effect in the sham group. Overall, our study showed that during prolonged pain, 5 days of 10 Hz rTMS induces a reduction in the TEP N45 peak. However, contrary to previous studies, prolonged pain itself did not increase the N45 peak. Taken together, this study provides weaker evidence for a link between the N45 peak and pain perception compared to previous research. Nonetheless, exploratory findings-such as a reduction in the N45 peak during the pain recovery phase and an individual-level relationship between increases in N45 and pain severity-suggest that further studies with larger sample sizes and more robust pain models are needed to clarify this connection.
最近使用经颅磁刺激（TMS）和脑电图（EEG）相结合的研究表明，疼痛会导致TMS诱发电位（TEP）的N45峰值增加，这可能与γ-氨基丁酸能活性的变化有关。相反，能缓解疼痛的10赫兹重复经颅磁刺激（10 Hz-rTMS）会降低N45峰值。然而，这些研究使用的是短暂的疼痛刺激（持续数分钟），限制了它们的临床相关性。本研究确定了在由向肘部肌肉注射神经生长因子（NGF）诱导的长期疼痛模型（持续数天）中，疼痛和10 Hz-rTMS对N45峰值的影响。在实验1中，对22名健康参与者在第0天（注射NGF前）、第2天（疼痛峰值）和第7天（疼痛恢复）测量TEP。在实验2中，我们研究了在NGF诱导的长期疼痛期间，对左侧初级运动皮层（M1）进行5天的主动（n = 16）或假（n = 16）rTMS对N45峰值的影响，并在第0天和第4天（rTMS后）测量TEP。在所有实验中，疼痛峰值和肌肉酸痛均为轻度至中度。在实验1中，没有证据表明在长期疼痛期间N45峰值会增加。探索性分析显示，有证据表明从第2天到第7天N45峰值降低，并且第2天较高的疼痛严重程度与N45峰值的较大增加之间存在相关性。在实验2中，主动rTMS使第4天的N45峰值相对于第0天降低，假刺激组则无此效果。总体而言，我们的研究表明，在长期疼痛期间，5天的10 Hz rTMS会导致TEP的N45峰值降低。然而，与先前的研究相反，长期疼痛本身并未增加N45峰值。综上所述，与先前的研究相比，本研究为N45峰值与疼痛感知之间的联系提供的证据较弱。尽管如此，探索性研究结果——如疼痛恢复阶段N45峰值降低以及N45增加与疼痛严重程度之间的个体水平关系——表明需要进行更大样本量和更稳健疼痛模型的进一步研究来阐明这种联系。
