ArticleCell reports2016
Sustained Elevated Adenosine via ADORA2B Promotes Chronic Pain through Neuro-immune Interaction.
Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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
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Who cites it
43 citing papers in PubMed, 68 citations in OpenAlex.
- Adenosine A2A signaling in mood disorders: How far have we come?IBRO neuroscience reports · 2025Article
- Widespread and prolonged pain may reduce brain clearance capacity only via sleep impairment: Evidence from participants with knee pain.The journal of pain · 2025Article
- APurinergic signalling · 2025Review
- Tmem45b modulates itch via endoplasmic reticulum calcium regulation.Frontiers in physiology · 2025Article
- Chaperone Copolymer-Assisted Catalytic Hairpin Assembly for Highly Sensitive Detection of Adenosine.Polymers · 2024Article
- Genomic evidence for the suitability of Göttingen Minipigs with a rare seizure phenotype as a model for human epilepsy.Neurogenetics · 2024Article
- A statistical method for image-mediated association studies discovers genes and pathways associated with four brain disorders.American journal of human genetics · 2024Article
- Predicting 'pain genes': multi-modal data integration using probabilistic classifiers and interaction networks.Bioinformatics advances · 2024Article
- Migraine signaling pathways: purine metabolites that regulate migraine and predispose migraineurs to headache.Molecular and cellular biochemistry · 2023Review
- Multi-Functional Small Molecule Alleviates Fracture Pain and Promotes Bone Healing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Adenosine receptor A2b confers ovarian cancer survival and PARP inhibitor resistance through IL-6-STAT3 signalling.Journal of cellular and molecular medicine · 2023Article
- Adenosine signaling mediate pain transmission in the central nervous system.Purinergic signalling · 2023Review
- Machine Learning and Pathway Analysis-Based Discovery of Metabolomic Markers Relating to Chronic Pain Phenotypes.International journal of molecular sciences · 2022Article
- Therapeutic Potential of Highly Selective AMolecules (Basel, Switzerland) · 2022Review
- Anti-Inflammatory Metabolites in the Pathogenesis of Bacterial Infection.Frontiers in cellular and infection microbiology · 2022Review
- Uncovering the Mechanisms of Adenosine Receptor-Mediated Pain Control: Focus on the AInternational journal of molecular sciences · 2021Review
- Novel curcumin analog (cis-trans curcumin) as ligand to adenosine receptors APharmacological research · 2021Article
- Comparing Efficacy and Safety of Empirical vs. Guided Therapy for Non-cardiac Chest Pain: A Pragmatic Randomized Trial.Frontiers in medicine · 2021Article
- Targeting Adenosine Receptors: A Potential Pharmacological Avenue for Acute and Chronic Pain.International journal of molecular sciences · 2020Review
- Purinergic Signaling in Endometriosis-Associated Pain.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
22 authors at 4 institutions in 2 countries.
Funding
Abstract
The molecular mechanisms of chronic pain are poorly understood and effective mechanism-based treatments are lacking. Here, we report that mice lacking adenosine deaminase (ADA), an enzyme necessary for the breakdown of adenosine, displayed unexpected chronic mechanical and thermal hypersensitivity due to sustained elevated circulating adenosine. Extending from Ada(-/-) mice, we further discovered that prolonged elevated adenosine contributed to chronic pain behaviors in two additional independent animal models: sickle cell disease mice, a model of severe pain with limited treatment, and complete Freund's adjuvant paw-injected mice, a well-accepted inflammatory model of chronic pain. Mechanistically, we revealed that activation of adenosine A2B receptors on myeloid cells caused nociceptor hyperexcitability and promoted chronic pain via soluble IL-6 receptor trans-signaling, and our findings determined that prolonged accumulated circulating adenosine contributes to chronic pain by promoting immune-neuronal interaction and revealed multiple therapeutic targets.
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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.