Pongratz G
Poliklink, Funktionsbereich und Hiller Forschungszentrum für Rheumatologie, Universitätsklinikum Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Deutschland.
Z Rheumatol. 2021 Apr;80(3):214-225. doi: 10.1007/s00393-020-00957-2. Epub 2021 Jan 14.
Persistent pain despite adequate inflammation control poses a big challenge in many rheumatic diseases for patients as well as physicians. The focus of drug development over the past years was on anti-inflammatory therapies. Enormous progress has been made and several treatment options have been added. It has been observed that pain triggered by inflammation can be effectively treated by inflammation control; however, the chronic pain component remains a problem, is little studied and specific treatment options are missing. Pain is influenced by inflammatory mediators, such as cytokines, which act on peripheral nociceptors and lead to peripheral sensitization. If inflammation continues, this can potentially lead to central sensitization and chronification of pain via immigration of immune cells and/or local activation of e.g. microglia. This leads to increasing autonomization and uncoupling of pain from the actual inflammatory process. The present review deals with the question if bDMARD or tsDMARD also show benefits concerning pain processes in addition to the profound inhibitory effects on inflammation. There are preclinical data that show an influence on sensitization following the use of cytokine inhibitors. On the other hand, so far clinical data show that bDMARDs as well as tsDMARDs consistently rapidly and reliably reduce nociceptive inflammatory pain across disease entities. An effect especially on the process of central sensitization and therefore on chronification of pain cannot be finally evaluated based on the currently available data.
尽管炎症得到了充分控制,但持续性疼痛对许多风湿性疾病的患者和医生来说都是一个巨大的挑战。在过去几年中,药物研发的重点是抗炎疗法。已经取得了巨大进展,并增加了几种治疗选择。据观察,由炎症引发的疼痛可以通过控制炎症得到有效治疗;然而,慢性疼痛成分仍然是一个问题,研究较少且缺乏具体的治疗选择。疼痛受炎症介质(如细胞因子)的影响,这些介质作用于外周伤害感受器并导致外周敏化。如果炎症持续,这可能会通过免疫细胞的迁移和/或例如小胶质细胞的局部激活,潜在地导致中枢敏化和疼痛的慢性化。这导致疼痛越来越自主化,并与实际的炎症过程脱钩。本综述探讨了一个问题,即除了对炎症有深刻的抑制作用外,生物性疾病修饰抗风湿药物(bDMARD)或靶向合成性疾病修饰抗风湿药物(tsDMARD)在疼痛过程方面是否也有益处。有临床前数据表明,使用细胞因子抑制剂后对敏化有影响。另一方面,到目前为止的临床数据表明,bDMARD和tsDMARD在各种疾病中都能持续、快速且可靠地减轻伤害性炎性疼痛。基于目前可用的数据,无法最终评估其对中枢敏化过程以及因此对疼痛慢性化的影响。