Pain is one of the most debilitating symptoms of rheumatoid arthritis (RA), and yet remains poorly understood, especially when pain occurs in the absence of synovitis. Without active inflammation, experts most often attribute joint pain to central nervous system dysfunction. However, advances in the past 5 years in both immunology and neuroscience research suggest that chronic pain in RA is also driven by a variety of abnormal interactions between peripheral neurons and mediators produced by resident cells in the local joint environment. In this Review, we discuss these novel insights from an interdisciplinary neuro-immune perspective. We outline a potential working model for the peripheral drivers of pain in RA, which includes autoantibodies, resident immune and mesenchymal cells and their interactions with different subtypes of peripheral sensory neurons. We also offer suggestions for how future collaborative research could be designed to accelerate analgesic drug development.

疼痛是类风湿性关节炎 （RA） 最令人衰弱的症状之一，但仍然知之甚少，尤其是当疼痛在没有滑膜炎的情况下发生时。如果没有活动性炎症，专家最常将关节疼痛归因于中枢神经系统功能障碍。然而，过去 5 年免疫学和神经科学研究的进展表明，RA 中的慢性疼痛也是由周围神经元与局部关节环境中常驻细胞产生的介质之间的各种异常相互作用驱动的。在这篇综述中，我们从跨学科神经免疫的角度讨论了这些新的见解。我们概述了 RA 中疼痛的外周驱动因素的潜在工作模型，其中包括自身抗体、常驻免疫细胞和间充质细胞以及它们与不同亚型的外周感觉神经元的相互作用。我们还就如何设计未来的合作研究来加速镇痛药的开发提供了建议。