To provide a historical perspective and narrative review on research into the molecular pathogenesis of osteoarthritis pain. PubMed databases were searched for combinations of “osteoarthritis”, “pain” and “animal models” for papers that represented key phases in the history of osteoarthritis pain discovery research including epidemiology, pathology, imaging, preclinical modeling and clinical trials. The possible anatomical sources of osteoarthritis pain were identified over 50 years ago, but relatively slow progress has been made in understanding the apparent disconnect between structural changes captured by radiography and symptom severity. Translationally relevant animal models of osteoarthritis have aided in our understanding of the structural and molecular drivers of osteoarthritis pain, including molecules such as nerve growth factor and C-C motif chemokine ligand 2. Events leading to persistent osteoarthritis pain appear to involve a two-step process involving changes in joint innervation, including neo-innervation of the articular cartilage, as well as sensitization at the level of the joint, dorsal root ganglion and central nervous system. There remains a great need for the development of treatments to reduce osteoarthritis pain in patients. Harnessing all that we have learned over the past several decades is helping us to appreciate the important interaction between structural disease and pain, and this is likely to facilitate development of new disease modifying therapies in the future.

中文翻译：

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OA 疼痛的分子发病机制：过去、现在和未来

为骨关节炎疼痛的分子发病机制研究提供历史视角和叙述性回顾。在 PubMed 数据库中搜索了“骨关节炎”、“疼痛”和“动物模型”的组合，以查找代表骨关节炎疼痛发现研究历史关键阶段的论文，包括流行病学、病理学、影像学、临床前建模和临床试验。 50 多年前就已经确定了骨关节炎疼痛可能的解剖学来源，但在理解放射线照相所捕获的结构变化与症状严重程度之间的明显脱节方面进展相对缓慢。骨关节炎的转化相关动物模型有助于我们了解骨关节炎疼痛的结构和分子驱动因素，包括神经生长因子和 CC 基序趋化因子配体 2 等分子。导致持续性骨关节炎疼痛的事件似乎涉及两个步骤，其中包括关节神经支配的变化，包括关节软骨的新神经支配，以及关节、背根神经节和中枢神经系统水平的敏化。仍然非常需要开发减轻患者骨关节炎疼痛的治疗方法。利用我们在过去几十年中学到的所有知识，正在帮助我们认识到结构性疾病和疼痛之间的重要相互作用，这可能会促进未来新的疾病修饰疗法的开发。