Repetitive transcranial magnetic stimulation (rTMS) is a promising technology to reduce chronic pain. Investigating the mechanisms of rTMS analgesia holds the potential to improve treatment efficacy. Using a double-blind and placebo-controlled design at both stimulation and pharmacologic ends, this study investigated the opioidergic mechanisms of rTMS analgesia by abolishing and recovering analgesia in 2 separate stages across brain regions and TMS doses. A group of 45 healthy participants were equally randomized to the primary motor cortex (M1), the dorsolateral prefrontal cortex (DLPFC), and the Sham group. In each session, participants received an intravenous infusion of naloxone or saline before the first rTMS session. Participants then received a second dose of rTMS session after the drugs were metabolized at 90 minutes. M1-rTMS-induced analgesia was abolished by naloxone compared with saline and was recovered by the second rTMS run when naloxone was metabolized. In the DLPFC, double but not the first TMS session induced significant pain reduction in the saline condition, resulting in less pain compared with the naloxone condition. In addition, TMS over the M1 or DLPFC selectively increased plasma concentrations of β-endorphin or encephalin, respectively. Overall, we present causal evidence that opioidergic mechanisms are involved in both M1-induced and DLPFC-rTMS-induced analgesia; however, these are shaped by rTMS dosage and the release of different endogenous opioids.

中文翻译：

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描述重复经颅磁刺激诱导镇痛的阿片类机制：一项随机对照试验。

重复经颅磁刺激（rTMS）是一种有前途的减轻慢性疼痛的技术。研究 rTMS 镇痛机制有可能提高治疗效果。本研究在刺激端和药理学端均采用双盲和安慰剂对照设计，通过跨脑区和 TMS 剂量分 2 个不同阶段废除和恢复镇痛，研究了 rTMS 镇痛的阿片类药物机制。 45 名健康参与者随机分为初级运动皮层 (M1)、背外侧前额叶皮层 (DLPFC) 和假手术组。在每次会议中，参与者在第一次 rTMS 会议之前接受静脉输注纳洛酮或盐水。药物在 90 分钟代谢后，参与者接受第二剂 rTMS 治疗。与生理盐水相比，M1-rTMS 诱导的镇痛被纳洛酮消除，并在纳洛酮代谢后通过第二次 rTMS 运行恢复。在 DLPFC 中，两次（而非第一次）TMS 治疗在盐水条件下显着减轻疼痛，与纳洛酮条件相比，疼痛减轻。此外，TMS 相对于 M1 或 DLPFC 选择性地分别增加 β-内啡肽或脑啡肽的血浆浓度。总体而言，我们提供了因果证据表明阿片样物质机制参与 M1 诱导和 DLPFC-rTMS 诱导的镇痛；然而，这些是由 rTMS 剂量和不同内源性阿片类药物的释放决定的。