Ciampi de Andrade Daniel, Valiengo Leandro
Department of Health Science and Technology, Faculty of Medicine, Center for Neuroplasticity and Pain (CNAP), Aalborg University, Aalborg, Denmark.
Interdisciplinary Neuromodulation Service (SIN), Department and Institute of Psychiatry, Faculty of Medicine, Hospital das Clínicas HCFMUSP, Universidade de São Paulo, São Paulo, Brazil.
Eur J Pain. 2025 Aug;29(7):e70077. doi: 10.1002/ejp.70077.
Chronic pain and major depressive disorder (MDD) are among the most prevalent and disabling conditions globally, often co-occurring and sharing overlapping symptoms such as fatigue, cognitive dysfunction and mood disturbances. While fibromyalgia, a primary pain syndrome, and MDD have distinct clinical manifestations, their comorbidity presents therapeutic challenges. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, has shown efficacy in treating both pain and mood disorders when targeted at specific brain regions (motor cortex for pain, dorsolateral prefrontal cortex for mood). This review aimed to investigate whether rTMS interventions for fibromyalgia or MDD improve symptoms across both domains, particularly in comorbid cases.
A structured search of PubMed was conducted between January and February 2025. Clinical trials were included if they were randomised, peer-reviewed, in English and involved ≥ 30 participants. Studies included addressed rTMS effects on pain in MDD or mood in fibromyalgia, or both. Out of 143 identified articles, 36 met the inclusion criteria.
Evidence shows rTMS has target- and symptom-specific effects: Motor cortex stimulation improves pain without reliably affecting mood, while dorsolateral prefrontal cortex stimulation alleviates depressive symptoms but inconsistently influences pain. These outcomes suggest that symptom improvement with rTMS is not global over different symptom clusters, but rather different for specific syndromes and the respective neural networks engaged by therapy. Personalised treatment strategies guided by pre-treatment connectivity profiles and symptom clusters, already in use for psychiatric disorders, could enhance outcomes in chronic pain management. However, limitations include small sample sizes, low session numbers and potential floor effects in studies involving non-depressed fibromyalgia patients.
Noninvasive neuromodulation therapy with repetitive transcranial magnetic stimulation for chronic pain improves pain on fibromyalgia and neuropathic pain but does not improve mood symptoms significantly. Therapy targeting mood symptoms in people with major depressive disorder may have antinociceptive effects in experimental pain models but are not clearly detectable in instances of clinical pain. The relationship between a disease and its associated symptoms is not linear or monotonic and differ between individuals. Unrevealing the associations between individual changes in brain connectivity during disease and the emergence of symptoms is central for the design of personalized and more effective therapeutic interventions.
慢性疼痛和重度抑郁症（MDD）是全球最普遍且使人丧失能力的病症，常常同时出现并伴有疲劳、认知功能障碍和情绪紊乱等重叠症状。虽然纤维肌痛（一种原发性疼痛综合征）和MDD有不同的临床表现，但它们的共病带来了治疗挑战。重复经颅磁刺激（rTMS）是一种非侵入性神经调节技术，当针对特定脑区（疼痛时针对运动皮层，情绪时针对背外侧前额叶皮层）时，已显示出对疼痛和情绪障碍均有疗效。本综述旨在研究针对纤维肌痛或MDD的rTMS干预是否能改善这两个领域的症状，尤其是在共病情况下。
于2025年1月至2月对PubMed进行了结构化检索。纳入的临床试验需为随机、经过同行评审、英文撰写且涉及≥30名参与者。纳入的研究涉及rTMS对MDD疼痛或纤维肌痛情绪的影响，或两者皆有。在143篇识别出的文章中，36篇符合纳入标准。
证据表明rTMS具有靶点和症状特异性效应：刺激运动皮层可改善疼痛但对情绪无可靠影响，而刺激背外侧前额叶皮层可缓解抑郁症状但对疼痛的影响不一致。这些结果表明，rTMS对不同症状群的症状改善并非全局性的，而是针对特定综合征及治疗所涉及的各自神经网络有所不同。在精神疾病治疗中已采用的，以治疗前连接图谱和症状群为指导的个性化治疗策略，可能会提高慢性疼痛管理的效果。然而，局限性包括样本量小、疗程数少以及在涉及非抑郁性纤维肌痛患者的研究中可能存在的底线效应。
重复经颅磁刺激的非侵入性神经调节疗法用于慢性疼痛时可改善纤维肌痛和神经性疼痛的疼痛症状，但对情绪症状改善不显著。针对重度抑郁症患者情绪症状的疗法在实验性疼痛模型中可能具有抗伤害感受作用，但在临床疼痛情况下并不明显可检测到。疾病与其相关症状之间的关系不是线性或单调的，且因人而异。揭示疾病期间大脑连接的个体变化与症状出现之间的关联对于设计个性化和更有效的治疗干预至关重要。
