ArticleJournal of neuroinflammation2017
Prophylactic inhibition of neutrophil elastase prevents the development of chronic neuropathic pain in osteoarthritic mice.
Article in Journal of neuroinflammation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 59 citations in OpenAlex.
- Effect of Pressure-Controlled Ventilation-Volume Guaranteed on One-Lung Ventilation in Elderly Patients Undergoing Thoracotomy.Medical science monitor : international medical journal of experimental and clinical research · 2020Trial
- Synovial fluid biomarkers associated with osteoarthritis severity reflect macrophage and neutrophil related inflammation.Arthritis research & therapy · 2019Trial
- Characterization of a mouse model to study mechanisms of hemophilia A pain.Blood advances · 2026Article
- Human α1-Antitrypsin Inhibits Nociceptor Excitability and Relieves Inflammatory and Neuropathic Pain.Biomolecules · 2026Article
- Efficacy and safety of sivelestat sodium hydrate adjunct to remifentanil for analgesia in patients under mechanical ventilation (SIDING trial): protocol of a multicenter, randomized, double-blinded, placebo-controlled trial.Frontiers in medicine · 2026Article
- Post-Herpetic Neuralgia: Review of Pathophysiology, Mechanisms, and Drug Treatment.Current neuropharmacology · 2026Review
- Proteomic analysis of spinal dorsal horn in prior exercise protection against neuropathic pain.Scientific reports · 2025Article
- Acetyl-11-keto-beta-boswellic acid ameliorates monosodium iodoacetate-induced osteoarthritis in rats: implications of HMGB1/TLR4/NF-κB and Nrf2/HO-1.Frontiers in pharmacology · 2025Article
- Neural and immune roles in osteoarthritis pain: Mechanisms and intervention strategies.Journal of orthopaedic translation · 2024Review
- CC Chemokine Family Members' Modulation as a Novel Approach for Treating Central Nervous System and Peripheral Nervous System Injury-A Review of Clinical and Experimental Findings.International journal of molecular sciences · 2024Review
- Inflammatory biomarkers and state of the tibiofemoral joint in the osteoarthritic knee: a narrative review.Annals of joint · 2024Review
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- Intervertebral disc degeneration and osteoarthritis: a common molecular disease spectrum.Nature reviews. Rheumatology · 2023Review
- Osteoarthritis: Pathogenesis, Animal Models, and New Regenerative Therapies.Journal of clinical medicine · 2022Review
- Osteoarthritis Pain in Old Mice Aggravates Neuroinflammation and Frailty: The Positive Effect of Morphine Treatment.Biomedicines · 2022Article
- The Effect and Mechanism of Lipoxin A4 on Neutrophil Function in LPS-Induced Lung Injury.Inflammation · 2022Article
- Single-Cell Landscape of Lungs Reveals Key Role of Neutrophil-Mediated Immunopathology during Lethal SARS-CoV-2 Infection.Journal of virology · 2022Article
- Imaging Study on Acupuncture Inhibiting Inflammation and Bone Destruction in Knee Osteoarthritis Induced by Monosodium Iodoacetate in Rat Model.Journal of pain research · 2022Article
- Joint Damage and Neuropathic Pain in Rats Treated With Lysophosphatidic Acid.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA subset of osteoarthritis (OA) patients experience joint pain with neuropathic characteristics. Mediators such as neutrophil elastase, a serine proteinase, may be released during acute OA inflammatory flares. We have previously shown that local administration of neutrophil elastase causes joint inflammation and pain via activation of proteinase-activated receptor-2 (PAR2). The aim of this study was to examine the contribution of endogenous neutrophil elastase and PAR2 to the development of joint inflammation, pain, and neuropathy associated with monoiodoacetate (MIA)-induced experimental OA.
methodsMIA (0.3 mg/10 μl) was injected into the right knee joint of male C57BL/6 mice (20-34 g). Joint inflammation (edema, leukocyte kinetics), neutrophil elastase proteolytic activity, tactile allodynia, and saphenous nerve demyelination were assessed over 14 days post-injection. The effects of inhibiting neutrophil elastase during the early inflammatory phase of MIA (days 0 to 3) were determined using sivelestat (50 mg/kg i.p.) and serpinA1 (10 μg i.p.). Involvement of PAR2 in the development of MIA-induced joint inflammation and pain was studied using the PAR2 antagonist GB83 (5 μg i.p. days 0 to 1) and PAR2 knockout animals.
resultsMIA caused an increase in neutrophil elastase proteolytic activity on day 1 (P < 0.0001), but not on day 14. MIA also generated a transient inflammatory response which peaked on day 1 (P < 0.01) then subsided over the 2-week time course. Joint pain appeared on day 1 and persisted to day 14 (P < 0.0001). By day 14, the saphenous nerve showed signs of demyelination. Early treatment with sivelestat and serpinA1 blocked the proteolytic activity of neutrophil elastase on day 1 (P < 0.001), and caused lasting improvements in joint inflammation, pain, and saphenous nerve damage (P < 0.05). MIA-induced synovitis was reversed by early treatment with GB83 and attenuated in PAR2 knockout mice (P < 0.05). PAR2 knockout mice also showed reduced MIA-induced joint pain (P < 0.0001) and less nerve demyelination (P = 0.81 compared to saline control).
conclusionsNeutrophil elastase and PAR2 contribute significantly to the development of joint inflammation, pain, and peripheral neuropathy associated with experimental OA, suggesting their potential as therapeutic targets.
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