Department of Anaesthesiology, Intensive Care and Pain Medicine, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
HUS Diagnostic Center, Clinical Neurophysiology, Clinical Neurosciences, Helsinki University Hospital and University of Helsinki, Helsinki, Finland; BioMag Laboratory, HUS Diagnostic Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Neuromodulation. 2022 Jun;25(4):538-548. doi: 10.1111/ner.13496. Epub 2022 Feb 2.
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.
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.
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.
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.
中枢性卒中后疼痛（CPSP）是一种神经病理性疼痛，难以治疗。针对初级运动皮层（M1）的重复经颅磁刺激（rTMS）可以缓解这种情况，但并非所有患者都有反应。我们旨在评估一种有前途的替代 rTMS 靶点，即次级体感皮层（S2），用于 CPSP 的治疗。
这是一项前瞻性、随机、双盲、假刺激对照的三臂交叉试验，评估了针对 M1 和 S2 的导航 rTMS（nrTMS）（10 个疗程，每个疗程 5050 个脉冲，频率为 10 Hz）。参与者接受了疼痛、抑郁、焦虑、健康相关生活质量、上肢功能以及三个与可塑性相关的基因多态性（包括多巴胺 D2 受体（DRD2））的评估。我们在刺激前、刺激期间和一个月后监测疼痛强度和干扰，并进行了条件性疼痛调制测试，使用冷加压测试来评估下行抑制系统的疗效，该系统可能在疼痛控制中传递 TMS 效应。
我们对 73 名患者进行了预筛选，对 29 名患者进行了筛查，并纳入了 21 名患者，其中 17 名完成了试验。针对 S2 的 nrTMS 导致 17 名参与者中有 18%（3/17）的疼痛强度在长期（从基线到一个月随访）内降低了≥30%。所有刺激均对疼痛产生了短期效果（疼痛缓解 17-20%），M1、S2 或假刺激之间没有差异，表明存在强烈的安慰剂效应。只有针对 S2 的 nrTMS 导致了长期疼痛强度的显著降低（疼痛缓解 15%）。冷加压测试显著降低了 CPSP 疼痛强度（p=0.001），表明下行抑制控制功能正常。DRD2 T/T 纯合子基因型与 M1 刺激反应相关。
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。
