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 het...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.展开更多
Osteoarthritis(OA)is a debilitating degenerative disease affecting multiple joint tissues,including cartilage,bone,synovium,and adipose tissues.OA presents diverse clinical phenotypes and distinct molecular endotypes,...Osteoarthritis(OA)is a debilitating degenerative disease affecting multiple joint tissues,including cartilage,bone,synovium,and adipose tissues.OA presents diverse clinical phenotypes and distinct molecular endotypes,including inflammatory,metabolic,mechanical,genetic,and synovial variants.Consequently,innovative technologies are needed to support the development of effective diagnostic and precision therapeutic approaches.Traditional analysis of bulk OA tissue extracts has limitations due to technical constraints,causing challenges in the differentiation between various physiological and pathological phenotypes in joint tissues.This issue has led to standardization difficulties and hindered the success of clinical trials.Gaining insights into the spatial variations of the cellular and molecular structures in OA tissues,encompassing DNA,RNA,metabolites,and proteins,as well as their chemical properties,elemental composition,and mechanical attributes,can contribute to a more comprehensive understanding of the disease subtypes.Spatially resolved biology enables biologists to investigate cells within the context of their tissue microenvironment,providing a more holistic view of cellular function.Recent advances in innovative spatial biology techniques now allow intact tissue sections to be examined using various-omics lenses,such as genomics,transcriptomics,proteomics,and metabolomics,with spatial data.This fusion of approaches provides researchers with critical insights into the molecular composition and functions of the cells and tissues at precise spatial coordinates.Furthermore,advanced imaging techniques,including high-resolution microscopy,hyperspectral imaging,and mass spectrometry imaging,enable the visualization and analysis of the spatial distribution of biomolecules,cells,and tissues.Linking these molecular imaging outputs to conventional tissue histology can facilitate a more comprehensive characterization of disease phenotypes.This review summarizes the recent advancements in the molecular imaging modalities and methodologies for in-depth spatial analysis.It explores their applications,challenges,and potential opportunities in the field of OA.Additionally,this review provides a perspective on the potential research directions for these contemporary approaches that can meet the requirements of clinical diagnoses and the establishment of therapeutic targets for OA.展开更多
基金supported by the National Health and Medical Research Council of Australia(No.APP1176298).
文摘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.
基金the NHMRC Investigator grant fellowship (APP1176298)the EMCR grant from the Centre for Biomedical Technologies (QUT)+4 种基金the QUT Postgraduate Research Award (QUTPRA)QUT HDR TOP-UP scholarshipQUT HDR Tuition Fee Sponsorshipfunding support from the Academy of Finland (315820)the Jane and Aatos Erkko Foundation (190001).
文摘Osteoarthritis(OA)is a debilitating degenerative disease affecting multiple joint tissues,including cartilage,bone,synovium,and adipose tissues.OA presents diverse clinical phenotypes and distinct molecular endotypes,including inflammatory,metabolic,mechanical,genetic,and synovial variants.Consequently,innovative technologies are needed to support the development of effective diagnostic and precision therapeutic approaches.Traditional analysis of bulk OA tissue extracts has limitations due to technical constraints,causing challenges in the differentiation between various physiological and pathological phenotypes in joint tissues.This issue has led to standardization difficulties and hindered the success of clinical trials.Gaining insights into the spatial variations of the cellular and molecular structures in OA tissues,encompassing DNA,RNA,metabolites,and proteins,as well as their chemical properties,elemental composition,and mechanical attributes,can contribute to a more comprehensive understanding of the disease subtypes.Spatially resolved biology enables biologists to investigate cells within the context of their tissue microenvironment,providing a more holistic view of cellular function.Recent advances in innovative spatial biology techniques now allow intact tissue sections to be examined using various-omics lenses,such as genomics,transcriptomics,proteomics,and metabolomics,with spatial data.This fusion of approaches provides researchers with critical insights into the molecular composition and functions of the cells and tissues at precise spatial coordinates.Furthermore,advanced imaging techniques,including high-resolution microscopy,hyperspectral imaging,and mass spectrometry imaging,enable the visualization and analysis of the spatial distribution of biomolecules,cells,and tissues.Linking these molecular imaging outputs to conventional tissue histology can facilitate a more comprehensive characterization of disease phenotypes.This review summarizes the recent advancements in the molecular imaging modalities and methodologies for in-depth spatial analysis.It explores their applications,challenges,and potential opportunities in the field of OA.Additionally,this review provides a perspective on the potential research directions for these contemporary approaches that can meet the requirements of clinical diagnoses and the establishment of therapeutic targets for OA.
