Chronic musculoskeletal pain is highly prevalent and poses a significant personal, societal, and economic burden. Management of chronic musculoskeletal pain remains a challenge. Long-term use of common analgesic medications such as nonsteroidal anti-inflammatory drugs and opioids is associated with adverse events, and in the case of opioids, drug addiction. Additionally, many individuals do not experience sufficient pain relief with these therapeutic approaches. Thus, there is an urgent need to develop clinically efficacious and safe therapeutics for musculoskeletal pain. Recent advances in our understanding of musculoskeletal pain neurobiology have helped identify the role of neurotrophic factors, specifically, the glial cell line-derived neurotrophic factor (GDNF) family of ligands (GFL) and their associated signaling pathways. This review outlines our current understanding of the GFL signaling systems, discusses their role in inflammatory and chronic musculoskeletal pain and sensitivity, and comments on the analgesic therapeutic potential of targeting the GFL signaling system.

中文翻译：

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青蒿素/GFRα3 信号转导在肌肉骨骼疼痛中的新证据


慢性肌肉骨骼疼痛非常普遍，并造成严重的个人、社会和经济负担。慢性肌肉骨骼疼痛的管理仍然是一个挑战。长期使用常见的镇痛药物，如非甾体抗炎药和阿片类药物与不良事件有关，在阿片类药物的情况下，与药物成瘾有关。此外，许多人没有通过这些治疗方法充分缓解疼痛。因此，迫切需要开发临床有效且安全的肌肉骨骼疼痛治疗方法。我们对肌肉骨骼疼痛神经生物学的理解的最新进展有助于确定神经营养因子的作用，特别是神经胶质细胞系衍生的神经营养因子 （GDNF） 配体家族 （GFL） 及其相关的信号通路。本文综述概述了我们目前对 GFL 信号系统的理解，讨论了它们在炎症和慢性肌肉骨骼疼痛和敏感性中的作用，并评论了靶向 GFL 信号系统的镇痛治疗潜力。