ArticlePain2019
Adenosine A3 receptor activation inhibits pronociceptive N-type Ca2+ currents and cell excitability in dorsal root ganglion neurons.
Article in Pain, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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.
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Who cites it
35 citing papers in PubMed, 49 citations in OpenAlex.
- Mitochondrial AThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- 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
- The dorsal root ganglion as a target for neurorestoration in neuropathic pain.Neural regeneration research · 2024Review
- Article
- 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
- Species dependence of APurinergic signalling · 2023Review
- Adenosine Receptors as Potential Therapeutic Analgesic Targets.International journal of molecular sciences · 2023Review
- Adenosine signaling mediate pain transmission in the central nervous system.Purinergic signalling · 2023Review
- Adenosine AInternational journal of molecular sciences · 2022Article
- Characterization of Dual-Acting AACS pharmacology & translational science · 2022Article
- Therapeutic Potential of Highly Selective AMolecules (Basel, Switzerland) · 2022Review
- 2‑Cl‑IB‑MECA regulates the proliferative and drug resistance pathways, and facilitates chemosensitivity in pancreatic and liver cancer cell lines.International journal of molecular medicine · 2022Article
- Single-cell RNA sequencing reveals distinct transcriptional features of the purinergic signaling in mouse trigeminal ganglion.Frontiers in molecular neuroscience · 2022Article
- Dysregulated long noncoding RNAs in the brainstem of the DBA/1 mouse model of SUDEP.BMC genomics · 2021Article
- Uncovering the Mechanisms of Adenosine Receptor-Mediated Pain Control: Focus on the AInternational journal of molecular sciences · 2021Review
- Studying human nociceptors: from fundamentals to clinic.Brain : a journal of neurology · 2021Review
- Dexpramipexole Enhances KMolecular neurobiology · 2021Article
- Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Recently, studies have focused on the antihyperalgesic activity of the A3 adenosine receptor (A3AR) in several chronic pain models, but the cellular and molecular basis of this effect is still unknown. Here, we investigated the expression and functional effects of A3AR on the excitability of small- to medium-sized, capsaicin-sensitive, dorsal root ganglion (DRG) neurons isolated from 3- to 4-week-old rats. Real-time quantitative polymerase chain reaction experiments and immunofluorescence analysis revealed A3AR expression in DRG neurons. Patch-clamp experiments demonstrated that 2 distinct A3AR agonists, Cl-IB-MECA and the highly selective MRS5980, inhibited Ca-activated K (KCa) currents evoked by a voltage-ramp protocol. This effect was dependent on a reduction in Ca influx via N-type voltage-dependent Ca channels, as Cl-IB-MECA-induced inhibition was sensitive to the N-type blocker PD173212 but not to the L-type blocker, lacidipine. The endogenous agonist adenosine also reduced N-type Ca currents, and its effect was inhibited by 56% in the presence of A3AR antagonist MRS1523, demonstrating that the majority of adenosine's effect is mediated by this receptor subtype. Current-clamp recordings demonstrated that neuronal firing of rat DRG neurons was also significantly reduced by A3AR activation in a MRS1523-sensitive but PD173212-insensitive manner. Intracellular Ca measurements confirmed the inhibitory role of A3AR on DRG neuronal firing. We conclude that pain-relieving effects observed on A3AR activation could be mediated through N-type Ca channel block and action potential inhibition as independent mechanisms in isolated rat DRG neurons. These findings support A3AR-based therapy as a viable approach to alleviate pain in different pathologies.
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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.