Department of Anesthesiology, Pain Clinic, First Affiliated Hospital of USTC (Anhui Provincial Hospital), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China.
Menzies Institute for Medical Research, University of Tasmania, Private Bag 23, Hobart, TAS, 7000, Australia.
Curr Rheumatol Rep. 2021 Apr 24;23(5):29. doi: 10.1007/s11926-021-00997-w.
Chronic pain in osteoarthritis (OA) is characterized by pain sensitization, which involves both peripheral and central mechanisms. Studies suggest synovial macrophage and spinal microglia are implicated in pain sensitization in OA. We, therefore, reviewed the evidence of whether synovial macrophage and spinal microglia facilitated pain sensitization at diverse levels and how this event occurred in OA.
Peripherally, joint inflammation is now believed to be a source of OA-related pain. Synovial macrophages accumulate in OA inflamed synovium and display a pro-inflammatory phenotype. Abundant macrophage-derived pro-inflammatory cytokines and other pain-causing substance facilitate hyperexcitation of primary sensory neuron in OA-related pain. Thus, activated synovial macrophage was considered a predictor for phenotyping of OA pain clinically. In response to affected joint-derived strong nociception, aberrant neuronal excitability is often associated with the hyperactivity of microglia in the spinal dorsal horn, thereby leading to central sensitization. Hyperactivity of synovial macrophage and spinal microglia underlies the mechanisms of pain sensitization at the peripheral and central level in OA. This concept provides not only a clinically relevant strategy for identifying the phenotype of OA-related pain but also has the potential to develop individualized interventions for OA, particularly in those patients with hyperactivity of macrophage and microglia.
骨关节炎（OA）的慢性疼痛以痛觉敏感为特征，涉及外周和中枢机制。研究表明，滑膜巨噬细胞和脊髓小胶质细胞参与 OA 中的痛觉敏感。因此，我们综述了滑膜巨噬细胞和脊髓小胶质细胞是否在不同水平促进痛觉敏感以及这一事件在 OA 中如何发生的证据。
现在认为关节炎症是 OA 相关疼痛的一个来源。滑膜巨噬细胞在 OA 炎症滑膜中积累，并表现出促炎表型。丰富的巨噬细胞衍生的促炎细胞因子和其他引起疼痛的物质促进 OA 相关疼痛中初级感觉神经元的过度兴奋。因此，活化的滑膜巨噬细胞被认为是 OA 疼痛表型临床预测因子。对受累关节衍生的强烈伤害感受的反应，异常的神经元兴奋性常与脊髓背角中小胶质细胞的过度活跃有关，从而导致中枢敏化。滑膜巨噬细胞和脊髓小胶质细胞的过度活跃是 OA 中外周和中枢水平痛觉敏感的机制。这一概念不仅为识别 OA 相关疼痛的表型提供了一种具有临床相关性的策略，而且有可能为 OA 开发个体化干预措施，特别是对那些巨噬细胞和小胶质细胞过度活跃的患者。
