ArticleArthritis research & therapy2015
Differences in glutamate receptors and inflammatory cell numbers are associated with the resolution of pain in human rotator cuff tendinopathy.
Article in Arthritis research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 24 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Connective Tissue Matrix (CTM) for Rotator Cuff Tendinopathy: A Randomized Controlled Trial
Connective Tissue Matrix (CTM) Compared to Corticosteroid Injections: A Pilot Randomized Controlled Trial
Who cites it
24 citing papers in PubMed, 3 syntheses or guidelines pooled it, 42 citations in OpenAlex.
- Proteomic trajectories in human rotator cuff degeneration: a systematic review of immunohistochemical studies.Journal of orthopaedic surgery and research · 2026Pooled it
- Is neurogenic inflammation involved in tendinopathy? A systematic review.BMJ open sport & exercise medicine · 2023Pooled it
- A systematic review of inflammatory cells and markers in human tendinopathy.BMC musculoskeletal disorders · 2020Pooled it
- Different Achilles Tendon Pathologies Show Distinct Histological and Molecular Characteristics.International journal of molecular sciences · 2018Trial
- Sensing the skeleton: sensorineural regulation in bone.Nature reviews. Neuroscience · 2026Review
- Opioid-Induced Hyperalgesia and Inflammaging in the Management of Spine Pain: The Case for Genetically Directed Dopamine Homeostasis.International journal of spine surgery · 2025Article
- Preoperative nutritional status and obesity are associated with muscle atrophy and fatty infiltration in degenerative rotator cuff tears.Journal of orthopaedic surgery and research · 2025Article
- Erroneous Differentiation of Tendon Stem/Progenitor Cells in the Pathogenesis of Tendinopathy: Current Evidence and Future Perspectives.Stem cell reviews and reports · 2025Review
- Platelet-rich Plasma in Orthopedics: Unraveling Cellular Mechanisms, Therapeutic Potential, and Limitations : Platelet-rich Plasma in Orthopedics.Galen medical journal · 2025Review
- Large extracellular vesicles secreted by human iPSC-derived MSCs ameliorate tendinopathyBioactive materials · 2023Article
- Biomolecules Related to Rotator Cuff Pain: A Scoping Review.Biomolecules · 2022Article
- No differences in histopathological degenerative changes found in acute, trauma-related rotator cuff tears compared with chronic, nontraumatic tears.Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA · 2022Article
- Why Use Adipose-Derived Mesenchymal Stem Cells in Tendinopathic Patients: A Systematic Review.Pharmaceutics · 2022Review
- Inflammatory mechanisms linking obesity and tendinopathy.Journal of orthopaedic translation · 2021Review
- Tendinopathy.Nature reviews. Disease primers · 2021Review
- Transmodulation of Dopaminergic Signaling to Mitigate Hypodopminergia and Pharmaceutical Opioid-Induced Hyperalgesia.Current psychopharmacology · 2020Article
- Review: Emerging concepts in the pathogenesis of tendinopathy.The surgeon : journal of the Royal Colleges of Surgeons of Edinburgh and Ireland · 2017Review
- Glutamate signaling through the NMDA receptor reduces the expression of scleraxis in plantaris tendon derived cells.BMC musculoskeletal disorders · 2017Article
- Inflammatory mechanisms in tendinopathy - towards translation.Nature reviews. Rheumatology · 2017Review
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
introductionThe relationship between peripheral tissue characteristics and pain symptoms in soft tissue inflammation is poorly understood. The primary aim of this study was to determine immunohistochemical differences in tissue obtained from patients with persistent pain and patients who had become pain-free after surgical treatment for rotator cuff tendinopathy. The secondary aim was to investigate whether there would be differences in glutaminergic and inflammatory gene expression between disease-derived and healthy control cells in vitro.
methodsSupraspinatus tendon biopsies were obtained from nine patients with tendon pain before shoulder surgery and from nine further patients whose pain had resolved completely following shoulder surgery. Histological markers relating to the basic tendon characteristics, inflammation and glutaminergic signalling were quantified by immunohistochemical analysis. Gene expression of glutaminergic and inflammatory markers was determined in tenocyte explants derived from painful rotator cuff tendon tears in a separate cohort of patients and compared to that of explants from healthy control tendons. Dual labelling was performed to identify cell types expressing nociceptive neuromodulators.
resultsTendon samples from patients with persistent pain demonstrated increased levels of metabotropic glutamate receptor 2 (mGluR2), kainate receptor 1 (KA1), protein gene product 9.5 (PGP9.5), CD206 (macrophage marker) and CD45 (pan-leucocyte marker) versus pain-free controls (p <0.05). NMDAR1 co-localised with CD206-positive cells, whereas PGP9.5 and glutamate were predominantly expressed by resident tendon cells. These results were validated by in vitro increases in the expression of mGluR2, N-methyl-D-aspartate receptor (NMDAR1), KA1, CD45, CD206 and tumour necrosis factor alpha (TNF-α) genes (p <0.05) in disease-derived versus control cells.
conclusionsWe conclude that differences in glutamate receptors and inflammatory cell numbers are associated with the resolution of shoulder pain in rotator cuff tendinopathy, and that disease-derived cells exhibit a distinctly different neuro-inflammatory gene expression profile to healthy control cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.