ArticleBrain : a journal of neurology2015
Endogenous adenosine A3 receptor activation selectively alleviates persistent pain states.
Article in Brain : a journal of neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
95 citing papers in PubMed, 1 synthesis or guideline pooled it, 140 citations in OpenAlex.
- Involvement of adenosine signaling pathway in migraine pathophysiology: a systematic review of preclinical studies.The journal of headache and pain · 2022Pooled it
- Special issue of Medicinal Chemistry Research in honor of Dr. Kenneth A. Jacobson.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
- Spinal cord stimulation: An emerging strategy for chronic pain relief after spinal cord injury.Neural regeneration research · 2026Article
- Neuropathic pain in traumatic brain injury: consequences, mechanisms, and therapeutic avenues.Inflammopharmacology · 2026Review
- Modulation of Spinal Mu-Opioid Receptor Expression by Selective Adenosine A1 and A3 Receptor Agonists and Allopurinol in a Rat Model of Neuropathic Pain.Medicina (Kaunas, Lithuania) · 2026Article
- A3 Adenosine Receptor Agonists as Multisystem Disease Modifiers: From Molecular Signaling to Clinical Translation.Biomolecules · 2026Review
- The therapeutic pipeline in migraine: What does the future hold?Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Review
- The cumulative analgesic effect of repeated electroacupuncture is modulated by Adora3 in the SCDH of mice with neuropathic pain.Animal models and experimental medicine · 2025Article
- Mechanism and modulation of spontaneous pain: from neural circuits to drug development.Molecular biology reports · 2025Review
- E. B. Hershberg Award: Taming Inflammation by Tuning Purinergic Signaling.Accounts of chemical research · 2025Article
- Engineered Delivery Systems for Chinese Herbal Medicine in Peripheral Nerve Regeneration: Challenges, Advances, and Future Perspectives.Drug design, development and therapy · 2025Review
- Potent and Selective Human 5-HTJournal of medicinal chemistry · 2024Article
- Electroacupuncture Relieves Neuropathic Pain via Adenosine 3 Receptor Activation in the Spinal Cord Dorsal Horn of Mice.International journal of molecular sciences · 2024Article
- Enhancing spinal cord stimulation-induced pain inhibition by augmenting endogenous adenosine signalling after nerve injury in rats.British journal of anaesthesia · 2024Article
- Covalently Binding Adenosine APurinergic signalling · 2024Article
- Purinergic Signaling and its Role in the Stem Cell Differentiation.Mini reviews in medicinal chemistry · 2024Review
- Multi-Functional Small Molecule Alleviates Fracture Pain and Promotes Bone Healing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Adenosine Receptors as Potential Therapeutic Analgesic Targets.International journal of molecular sciences · 2023Review
- Curcumin Stereoisomer, Cis-Trans Curcumin, as a Novel Ligand to APharmaceuticals (Basel, Switzerland) · 2023Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
Chronic pain is a global burden that promotes disability and unnecessary suffering. To date, efficacious treatment of chronic pain has not been achieved. Thus, new therapeutic targets are needed. Here, we demonstrate that increasing endogenous adenosine levels through selective adenosine kinase inhibition produces powerful analgesic effects in rodent models of experimental neuropathic pain through the A3 adenosine receptor (A3AR, now known as ADORA3) signalling pathway. Similar results were obtained by the administration of a novel and highly selective A3AR agonist. These effects were prevented by blockade of spinal and supraspinal A3AR, lost in A3AR knock-out mice, and independent of opioid and endocannabinoid mechanisms. A3AR activation also relieved non-evoked spontaneous pain behaviours without promoting analgesic tolerance or inherent reward. Further examination revealed that A3AR activation reduced spinal cord pain processing by decreasing the excitability of spinal wide dynamic range neurons and producing supraspinal inhibition of spinal nociception through activation of serotonergic and noradrenergic bulbospinal circuits. Critically, engaging the A3AR mechanism did not alter nociceptive thresholds in non-neuropathy animals and therefore produced selective alleviation of persistent neuropathic pain states. These studies reveal A3AR activation by adenosine as an endogenous anti-nociceptive pathway and support the development of A3AR agonists as novel therapeutics to treat chronic pain.
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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.