ArticleThe Journal of clinical investigation2021
Adenosine A3 agonists reverse neuropathic pain via T cell-mediated production of IL-10.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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The trial behind it
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Who cites it
47 citing papers in PubMed, 68 citations in OpenAlex.
- Targeting GCell reports. Medicine · 2026Article
- T-cell distribution in the dorsal root ganglion across species, sex, and age.bioRxiv : the preprint server for biology · 2026Article
- The role of gut microbiota in neuropathic pain: insights into immune mechanisms.The journal of headache and pain · 2025Review
- Exercise facilitates post-stroke recovery through mitigation of neuronal hyperexcitability via interleukin-10 signaling.Nature communications · 2025Article
- Sex Differences in the Regulation of Interleukins in Chronic Pain: A Widely Recognized but Difficult-to-Tackle Factor.International journal of molecular sciences · 2025Review
- Upregulation of delta opioid receptor by meningeal interleukin-10 prevents relapsing pain.Brain, behavior, and immunity · 2025Article
- Potential of Adora2b as an immunotherapeutic target for gastric cancer.Frontiers in immunology · 2025Review
- α9-Containing Nicotinic Acetylcholine Receptors Are Required for RgIA-5474 Attenuation of Chemotherapy-Induced Neuropathic Pain.ACS pharmacology & translational science · 2024Article
- Gene therapy for chronic pain management.Cell reports. Medicine · 2024Review
- Adenosine and adenosine receptors in metabolic imbalance-related neurological issues.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Review
- Identification of Oxidative Stress-Related Biomarkers for Pain-Depression Comorbidity Based on Bioinformatics.International journal of molecular sciences · 2024Article
- Lipid Trolling to Optimize AJournal of medicinal chemistry · 2024Article
- Activation of hepatic adenosine A1 receptor ameliorates MASH via inhibiting SREBPs maturation.Cell reports. Medicine · 2024Article
- Covalently Binding Adenosine APurinergic signalling · 2024Article
- Roles of pyroptosis and immune infiltration in aortic dissection.Frontiers in molecular biosciences · 2024Article
- Targeting sensory neuron GPCRs for peripheral neuropathic pain.Trends in pharmacological sciences · 2023Review
- Multi-Functional Small Molecule Alleviates Fracture Pain and Promotes Bone Healing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Developmental impact of peripheral injury on neuroimmune signaling.Brain, behavior, and immunity · 2023Review
- Pharmacology of Adenosine Receptors: Recent Advancements.Biomolecules · 2023Review
- Species dependence of APurinergic signalling · 2023Review
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
The A3 adenosine receptor (A3AR) has emerged as a therapeutic target with A3AR agonists to tackle the global challenge of neuropathic pain, and investigation into its mode of action is essential for ongoing clinical development. Immune cell A3ARs, and their activation during pathology, modulate cytokine release. Thus, the use of immune cells as a cellular substrate for the pharmacological action of A3AR agonists is enticing, but unknown. The present study discovered that Rag-KO mice lacking T and B cells, as compared with WT mice, are insensitive to the anti-allodynic effects of A3AR agonists. Similar findings were observed in interleukin-10 and interleukin-10 receptor knockout mice. Adoptive transfer of CD4+ T cells from WT mice infiltrated the dorsal root ganglion (DRG) and restored A3AR agonist-mediated anti-allodynia in Rag-KO mice. CD4+ T cells from Adora3-KO or Il10-KO mice did not. Transfer of CD4+ T cells from WT mice, but not Il10-KO mice, into Il10-KO mice or Adora3-KO mice fully reinstated the anti-allodynic effects of A3AR activation. Notably, A3AR agonism reduced DRG neuron excitability when cocultured with CD4+ T cells in an IL-10-dependent manner. A3AR action on CD4+ T cells infiltrated in the DRG decreased phosphorylation of GluN2B-containing N-methyl-D-aspartate receptors at Tyr1472, a modification associated with regulating neuronal hypersensitivity. Our findings establish that activation of A3AR on CD4+ T cells to release IL-10 is required and sufficient evidence for the use of A3AR agonists as therapeutics.
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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.