Chowdhury Nahian S, Chang Wei-Ju, Cheng Donovan, Manivasagan Naveen, Seminowicz David A, Schabrun Siobhan M
bioRxiv. 2024 Nov 28:2024.11.26.625334. doi: 10.1101/2024.11.26.625334.
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.
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,这是由γ-氨基丁酸能抑制介导的。相反,能缓解疼痛的10Hz重复经颅磁刺激(10Hz-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10Hz-rTMS对N45峰值的影响。
实验1:在第0天(注射NGF前)、第2天(疼痛峰值)和第7天(疼痛缓解)对22名健康参与者测量TEP。实验2: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,在第0天和第4天(rTMS后)测量TEP。
实验1:虽然N45峰值没有总体变化,但第2天较高的疼痛严重程度与N45峰值的更大增加之间出现了相关性。实验2:与第0天相比,主动rTMS在第4天降低了N45峰值,假刺激组没有效果。
我们的研究结果表明,(i)较高的疼痛严重程度与N45峰值的增加相关,(ii)在长期实验性疼痛模型中,rTMS会降低皮层抑制。本研究通过证明在长期疼痛背景下疼痛感知与皮层抑制之间的联系,扩展了先前的研究。