Double-Cone Coil TMS Stimulation of the Medial Cortex Inhibits Central Pain Habituation

Objective
The aim of this study was to investigate whether Transcranial Magnetic Stimulation (TMS) applied over the medial line of the scalp affects the subjective perception of continuous pain induced by means of electric stimulation. In addition, we wanted to identify the point of stimulation where this effect was maximum.
Methods
Superficial electrical stimulation was used to induce continuous pain on the dominant hand. At the beginning of the experiment we reached a pain rating of 5 on an 11-point numeric rating scale (NRS; 0 = no pain and 10 = maximum tolerable pain) for each subject by setting individually the current intensity. The TMS (five pulses at increasing intensities) was applied on 5 equidistant points (one per session) over the medial line of the scalp in 13 healthy volunteers using a double-cone coil to stimulate underlying parts of the brain cortex. In every experimental session the painful stimulation lasted 45 minutes, during which pain and distress intensities NRS were recorded continuously. We calculated the effect of adaptation and the immediate effect of the TMS stimulation for all locations. Additionally, an ALE (Activation Likelihood Estimation) meta-analysis was performed to compare our results with the neuroimaging literature on subjective pain rating.
Results
TMS stimulation temporarily decreased the pain ratings, and pain adaptation was suppressed when applying the TMS over the FCz site on the scalp. No effect was found for distress ratings.
Conclusions
The present data suggest that the medial cortex in proximity of the cingulated gyrus has a causal role in adaptation mechanisms and in processing ongoing pain and subjective sensation of pain intensity.

### 研究目的
本研究旨在探究施加于头皮中线的经颅磁刺激（Transcranial Magnetic Stimulation, TMS）是否会对电刺激诱发的持续性疼痛的主观感知产生影响；此外，本研究还旨在确定该干预效应最强的刺激位点。

### 研究方法
本研究采用浅表电刺激于受试者利手处诱发持续性疼痛。实验初始阶段，我们通过个体化调整电流强度，使每位受试者在11点数字评分量表（Numeric Rating Scale, NRS；0分代表无痛，10分代表最大耐受疼痛）上的疼痛评分达到5分。本研究纳入13名健康志愿者，采用双锥线圈刺激大脑皮层深部结构，于头皮中线设置5个等距刺激位点（每轮实验对应一个位点），施加强度递增的5脉冲经颅磁刺激。每轮实验中，疼痛刺激持续45分钟，期间持续记录疼痛与痛苦强度的NRS评分。我们针对所有刺激位点，分别计算了疼痛适应效应与经颅磁刺激的即时效应。此外，本研究还开展了激活似然估计（Activation Likelihood Estimation, ALE）元分析，将本研究结果与主观疼痛评分相关的神经影像学文献进行对比。

### 研究结果
经颅磁刺激可暂时性降低疼痛评分；当刺激头皮FCz位点时，疼痛适应效应被抑制。未观察到该干预对痛苦评分产生显著影响。

### 研究结论
本研究数据表明，扣带回（cingulate gyrus）附近的内侧皮层在疼痛适应机制、持续性疼痛加工以及疼痛强度的主观感知中发挥因果性作用。