ArticleArthritis research & therapy2016
Selective inhibition of tropomyosin-receptor-kinase A (TrkA) reduces pain and joint damage in two rat models of inflammatory arthritis.
Article in Arthritis research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 63 citations in OpenAlex.
- Demonstration of an anti-hyperalgesic effect of a novel pan-Trk inhibitor PF-06273340 in a battery of human evoked pain models.British journal of clinical pharmacology · 2018Trial
- Single-nuclei RNA sequencing reveals distinct transcriptomic signatures of rat dorsal root ganglia in a chronic discogenic low back pain model.The journal of pain · 2026Article
- Platelet-rich plasma relieves inflammation and pain by regulating M1/M2 macrophage polarization in knee osteoarthritis rats.Scientific reports · 2025Article
- Pain mechanism and management strategy of rheumatoid arthritis.Frontiers in pain research (Lausanne, Switzerland) · 2025Review
- Transcriptome analysis of rheumatoid arthritis uncovers genes linked to inflammation-induced pain.Scientific reports · 2024Article
- Nerve Growth Factor Signaling Modulates the Expression of Glutaminase in Dorsal Root Ganglion Neurons during Peripheral Inflammation.International journal of molecular sciences · 2024Article
- Identifying therapeutic candidates for endometriosis through a transcriptomics-based drug repositioning approach.iScience · 2024Article
- Transcriptome Analysis of Rheumatoid Arthritis Uncovers Genes Linked to Inflammation-Induced Pain.Research square · 2024Article
- Upregulation of NGF/TrkA-Related Proteins in Dorsal Root Ganglion of Paclitaxel-Induced Peripheral Neuropathy Animal Model.Journal of pain research · 2024Article
- Variation of sexual dimorphism and asymmetry in disease expression of inflammatory arthritis among laboratory mouse models with different genomic backgrounds.Laboratory animal research · 2023Article
- Nerve Growth Factor and Autoimmune Diseases.Current issues in molecular biology · 2023Review
- Sensory Neuron-Specific Deletion of Tropomyosin Receptor Kinase A (International journal of molecular sciences · 2022Article
- Article
- Neuron-to-vessel signaling is a required feature of aberrant stem cell commitment after soft tissue trauma.Bone research · 2022Article
- Investigating the Role of Artemin and Its Cognate Receptor, GFRα3, in Osteoarthritis Pain.Frontiers in neuroscience · 2022Article
- Based on minimal clinically important difference values, a moderate dose of tanezumab may be a better option for treating hip or knee osteoarthritis: a meta-analysis of randomized controlled trials.Therapeutic advances in musculoskeletal disease · 2022Article
- In Pursuit of an Allosteric Human Tropomyosin Kinase A (ACS medicinal chemistry letters · 2021Article
- Monoclonal Antibodies for Chronic Pain Treatment: Present and Future.International journal of molecular sciences · 2021Review
- NGF-TrkA signaling dictates neural ingrowth and aberrant osteochondral differentiation after soft tissue trauma.Nature communications · 2021Article
- Dexamethasone-loaded thermo-sensitive hydrogel attenuates osteoarthritis by protecting cartilage and providing effective pain relief.Annals of translational medicine · 2021Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInflammation is an essential component of arthritis pain. Nerve growth factor (NGF) plays a key role in acute and chronic pain states especially those associated with inflammation. NGF acts through tropomyosin-receptor-kinase A (TrkA). NGF blockade has reduced arthritis pain in clinical trials. We explored the mechanisms within the joint which may contribute to the analgesic effects of NGF by selectively inhibiting TrkA in carrageenan-induced or collagen-induced joint pain behaviour. The goal of the current study was to elucidate whether inflammation is central to the efficacy for NGF blockade.
methodsRats were injected in their left knees with 2 % carrageenan or saline. Collagen-induced arthritis (CIA) was induced by intradermal injections of a mixture of bovine type II collagen (0.2 mg) and incomplete Freund's adjuvant (0.2 mg). Oral doses (30 mg/kg) of AR786 or vehicle control were given twice daily after arthritis induction. Ibuprofen-treated (35 mg/kg, orally, once daily) rats with CIA were used as positive analgesic controls. Pain behaviour was measured as hind-limb weight-bearing asymmetry and hind-paw withdrawal thresholds to von Frey hair stimulation (carrageenan synovitis), or withdrawal to joint compression using a Randall Selitto device (CIA). Inflammation was measured as increased knee joint diameter and by histopathological analysis.
resultsIntra-articular injections of carrageenan or induction of CIA was each associated with pain behaviour and synovial inflammation. Systemic administration of the TrkA inhibitor AR786 reduced carrageenan-induced or CIA-induced pain behaviour to control values, and inhibited joint swelling and histological evidence of synovial inflammation and joint damage.
conclusionsBy using two models of varying inflammation we demonstrate for the first time that selective inhibition of TrkA may reduce carrageenan-induced or CIA-induced pain behaviour in rats, in part through potentially inhibiting synovial inflammation, although direct effects on sensory nerves are also likely. Our observations suggest that inflammatory arthritis causes pain and the presence of inflammation is fundamental to the beneficial effects (reduction in pain and pathology) of NGF blockade. Further research should determine whether TrkA inhibition may ameliorate human inflammatory arthritis.
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