Gupta Ankita, Mishra Santosh K, Lascelles B Duncan X
Translational Research in Pain Program, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
Osteoarthritis Cartilage. 2025 Feb;33(2):196-206. doi: 10.1016/j.joca.2024.09.010. Epub 2024 Oct 5.
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.
慢性肌肉骨骼疼痛非常普遍，给个人、社会和经济带来了沉重负担。慢性肌肉骨骼疼痛的管理仍然是一项挑战。长期使用非甾体抗炎药和阿片类药物等常见镇痛药会引发不良事件，而就阿片类药物而言，还会导致药物成瘾。此外，许多人通过这些治疗方法无法获得足够的疼痛缓解。因此，迫切需要开发用于肌肉骨骼疼痛的临床有效且安全的治疗方法。我们对肌肉骨骼疼痛神经生物学认识的最新进展有助于确定神经营养因子的作用，特别是胶质细胞源性神经营养因子（GDNF）配体家族（GFL）及其相关信号通路的作用。本综述概述了我们目前对GFL信号系统的理解，讨论了它们在炎症性和慢性肌肉骨骼疼痛及敏感性中的作用，并对靶向GFL信号系统的镇痛治疗潜力进行了评论。
