Objectives

Central poststroke pain (CPSP), a neuropathic pain condition, is difficult to treat. Repetitive transcranial magnetic stimulation (rTMS) targeted to the primary motor cortex (M1) can alleviate the condition, but not all patients respond. We aimed to assess a promising alternative rTMS target, the secondary somatosensory cortex (S2), for CPSP treatment.

Materials and Methods

This prospective, randomized, double-blind, sham-controlled three-arm crossover trial assessed navigated rTMS (nrTMS) targeted to M1 and S2 (10 sessions, 5050 pulses per session at 10 Hz). Participants were evaluated for pain, depression, anxiety, health-related quality of life, upper limb function, and three plasticity-related gene polymorphisms including Dopamine D2 Receptor (DRD2). We monitored pain intensity and interference before and during stimulations and at one month. A conditioned pain modulation test was performed using the cold pressor test. This assessed the efficacy of the descending inhibitory system, which may transmit TMS effects in pain control.

Results

We prescreened 73 patients, screened 29, and included 21, of whom 17 completed the trial. NrTMS targeted to S2 resulted in long-term (from baseline to one-month follow-up) pain intensity reduction of ≥30% in 18% (3/17) of participants. All stimulations showed a short-term effect on pain (17–20% pain relief), with no difference between M1, S2, or sham stimulations, indicating a strong placebo effect. Only nrTMS targeted to S2 resulted in a significant long-term pain intensity reduction (15% pain relief). The cold pressor test reduced CPSP pain intensity significantly (p = 0.001), indicating functioning descending inhibitory controls. The homozygous DRD2 T/T genotype is associated with the M1 stimulation response.

Conclusions

S2 is a promising nrTMS target in the treatment of CPSP. The DRD2 T/T genotype might be a biomarker for M1 nrTMS response, but this needs confirmation from a larger study.

中文翻译：

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针对中枢性卒中后疼痛的 M1 和 S2 的重复经颅磁刺激的随机、假对照试验：一项试点试验

目标

中枢性卒中后疼痛 (CPSP) 是一种神经性疼痛，难以治疗。针对初级运动皮层 (M1) 的重复经颅磁刺激 (rTMS) 可以缓解病情，但并非所有患者都有反应。我们旨在评估用于 CPSP 治疗的有前景的替代 rTMS 靶标，即次级体感皮层 (S2)。

材料和方法

这项前瞻性、随机、双盲、假控制的三臂交叉试验评估了针对 M1 和 S2 的导航 rTMS (nrTMS)（10 个疗程，每次 5050 个脉冲，频率为 10 Hz）。评估参与者的疼痛、抑郁、焦虑、与健康相关的生活质量、上肢功能和三种可塑性相关的基因多态性，包括多巴胺 D2 受体 (DRD2)。我们在刺激之前和期间以及一个月时监测疼痛强度和干扰。使用冷加压试验进行条件性疼痛调节试验。这评估了下行抑制系统的功效，该系统可能在疼痛控制中传递 TMS 效应。

结果

我们预筛选了 73 名患者，筛选了 29 名患者，包括 21 名患者，其中 17 名完成了试验。针对 S2 的 NrTMS 导致 18% (3/17) 的参与者长期（从基线到 1 个月的随访）疼痛强度降低 ≥30%。所有刺激都显示出对疼痛的短期影响（17-20% 的疼痛缓解），M1、S2 或假刺激之间没有差异，表明安慰剂效应很强。只有针对 S2 的 nrTMS 导致长期疼痛强度显着降低（15% 的疼痛缓解）。冷加压试验显着降低了 CPSP 疼痛强度（p  = 0.001），表明功能下降的抑制控制。纯合DRD2 T/T 基因型与 M1 刺激反应相关。

结论

S2是治疗CPSP的有前途的nrTMS靶点。DRD2 T/T 基因型可能是 M1 nrTMS 反应的生物标志物，但这需要更大规模的研究来证实。