Understanding pain heterogeneity in osteoarthritis patients: a narrative review

Lin Li , Xiwei Fan , Ross Crawford , Xinzhan Mao , Louis Jun Ye Ong , Feng Gao , Antonia Rujia Sun , Indira Prasadam

Front. Med. ›› 2025, Vol. 19 ›› Issue (5) : 769 -788.

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Front. Med. ›› 2025, Vol. 19 ›› Issue (5) : 769 -788. DOI: 10.1007/s11684-025-1143-5
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Understanding pain heterogeneity in osteoarthritis patients: a narrative review

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Abstract

The primary clinical manifestation of osteoarthritis (OA) is pain, yet considerable variability exists in the pain experience among OA patients. This narrative review aims to explore the mechanisms driving OA pain heterogeneity to inform the development of targeted interventions that improve treatment efficacy and patient outcomes. A comprehensive literature search was conducted across multiple databases (PubMed, Scopus, and Google Scholar) for papers published between January 1, 2020, and December 31, 2024. Inclusion criteria focused on studies addressing pain mechanisms and therapeutic interventions in OA. This review identifies key mechanisms of OA pain, including joint alterations, angiogenesis, nervous system involvement, peripheral and central sensitization, and psychosocial factors. It highlights the underlying distinct mechanisms in OA pain, which contribute to the variability in individuals’ responses to treatment. It was suggested that interactions between neuroimmune and neurovascular systems are key contributors to chronic pain in OA. This narrative review emphasizes the complexity of OA pain, highlighting the importance of thoroughly understanding the underlying mechanisms for developing personalized and effective pain management strategies. Additional research is required to refine treatment approaches and explore long-term effects.

Keywords

osteoarthritis / pain / structural alteration / nervous system / psychosocial factors / therapeutics

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Lin Li, Xiwei Fan, Ross Crawford, Xinzhan Mao, Louis Jun Ye Ong, Feng Gao, Antonia Rujia Sun, Indira Prasadam. Understanding pain heterogeneity in osteoarthritis patients: a narrative review. Front. Med., 2025, 19(5): 769-788 DOI:10.1007/s11684-025-1143-5

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