ArticleOsteoarthritis and cartilage2020
Microarray analyses of the dorsal root ganglia support a role for innate neuro-immune pathways in persistent pain in experimental osteoarthritis.
Article in Osteoarthritis and cartilage, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- The causal effect of cytokine cycling levels on osteoarthritis: a bidirectional Mendelian randomized study.Frontiers in immunology · 2023Pooled it
- New Adjuvant Therapies for Obesity-Related Disorders Associated with Meta-Neuroinflammation.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Immunologic Profiling Suggests an Association Between Treg Cell Dysfunction and Pain in Knee Osteoarthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Borderline acceleration in blood epigenetic age of unclear biological importance in knee osteoarthritis progression: Specimens and data from the Osteoarthritis Initiative and Johnston County Osteoarthritis Project.Osteoarthritis and cartilage · 2026Article
- Chronic Oxaliplatin Treatment Induces CIPN in Mice via Activation of the TXNIP Pathway.Molecular neurobiology · 2025Article
- Understanding pain heterogeneity in osteoarthritis patients: a narrative review.Frontiers of medicine · 2025Review
- Sensory neuron-specific block of multifaceted sodium channels mitigates neuropathic pain behaviors of osteoarthritis.Pain reports · 2025Article
- Deciphering cartilage neuro-immune interactions and innervation profile through 3D engineered osteoarthritic micropathophysiological system.Materials today. Bio · 2025Article
- Emerging evidence of artemin/GFRα3 signaling in musculoskeletal pain.Osteoarthritis and cartilage · 2025Review
- Bromodomain and Extraterminal Protein Inhibition: A Novel Therapeutic Strategy in Arthritis.Journal of inflammation research · 2025Review
- Significant hindlimb static weight-bearing asymmetry persists for 40-weeks in a longitudinal study in two widely used rat models of surgically induced osteoarthritis knee pain.Frontiers in pharmacology · 2025Article
- The Role of Thrombospondins in Osteoarthritis: from Molecular Mechanisms to Therapeutic Potential.International journal of biological sciences · 2025Review
- Acute systemic macrophage depletion in osteoarthritic mice alleviates pain-related behaviors and does not affect joint damage.Arthritis research & therapy · 2024Article
- Brain Amyloid-β Peptide Is Associated with Pain Intensity and Cognitive Dysfunction in Osteoarthritic Patients.International journal of molecular sciences · 2024Observational
- Proteomic Analysis of Signaling Pathways Modulated by Fatty Acid Binding Protein 5 (FABP5) in Macrophages.The Journal of pharmacology and experimental therapeutics · 2024Article
- Acute systemic macrophage depletion in osteoarthritic mice alleviates pain-related behaviors and does not affect joint damage.bioRxiv : the preprint server for biology · 2024Article
- Fatty acid binding protein 5 inhibition attenuates pronociceptive cytokine/chemokine expression and suppresses osteoarthritis pain: A comparative human and rat study.Osteoarthritis and cartilage · 2024Article
- Human-specific duplicate CHRFAM7A gene is associated with more severe osteoarthritis and amplifies pain behaviours.Annals of the rheumatic diseases · 2023Article
- Notch signaling is activated in knee-innervating dorsal root ganglia in experimental models of osteoarthritis joint pain.Arthritis research & therapy · 2023Article
- Analysis of matrisome expression patterns in murine and human dorsal root ganglia.Frontiers in molecular neuroscience · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
objectiveFollowing destabilization of the medial meniscus (DMM), mice develop experimental osteoarthritis (OA) and associated pain behaviors that are dependent on the stage of disease. We aimed to describe changes in gene expression in knee-innervating dorsal root ganglia (DRG) after surgery, in order to identify molecular pathways associated with three pre-defined pain phenotypes: "post-surgical pain", "early-stage OA pain", and "persistent OA pain".
designWe performed DMM or sham surgery in 10-week old male C57BL/6 mice and harvested L3-L5 DRG 4, 8, and 16 weeks after surgery or from age-matched naïve mice (n = 3/group). RNA was extracted and an Affymetrix Mouse Transcriptome Array 1.0 was performed. Three pain phenotypes were defined: "post-surgical pain" (sham and DMM 4-week vs 14-week old naïve), "early OA pain" (DMM 4-week vs sham 4-week), and "persistent OA pain" (DMM 8- and 16-week vs naïve and sham 8- and 16-week). 'Top hit' genes were defined as P < 0.001. Pathway analysis (Ingenuity Pathway Analysis) was conducted using differentially expressed genes defined as P < 0.05. In addition, we performed qPCR for Ngf and immunohistochemistry for F4/80+ macrophages in the DRG.
resultsFor each phenotype, top hit genes identified a small number of differentially expressed genes, some of which have been previously associated with pain (7/67 for "post-surgical pain"; 2/14 for "early OA pain"; 8/37 for "persistent OA pain"). Overlap between groups was limited, with 8 genes differentially regulated (P < 0.05) in all three phenotypes. Pathway analysis showed that in the persistent OA pain phase many of the functions of differentially regulated genes are related to immune cell recruitment and activation. Genes previously linked to OA pain (CX3CL1, CCL2, TLR1, and NGF) were upregulated in this phenotype and contributed to activation of the neuroinflammation canonical pathway. In separate sets of mice, we confirmed that Ngf was elevated in the DRG 8 weeks after DMM (P = 0.03), and numbers of F4/80+ macrophages were increased 16 weeks after DMM (P = 0.002 vs Sham).
conclusionThese transcriptomics findings support the idea that distinct molecular pathways discriminate early from persistent OA pain. Pathway analysis suggests neuroimmune interactions in the DRG contribute to initiation and maintenance of pain in OA.
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