ArticlePain2016
Group II mGluRs suppress hyperexcitability in mouse and human nociceptors.
Article in Pain, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 62 citations in OpenAlex.
- Osteoarthritis: molecular pathogenesis and potential therapeutic options.Signal transduction and targeted therapy · 2026Review
- Suppression of neuropathic pain hypersensitivity by TRPM8 is mediated by mGluR group II and III receptors acting differentially on distinct nociceptor inputs to spinal cord.Frontiers in pharmacology · 2026Article
- Sensory neuron-expressed FGF13 controls nociceptive signaling in diabetic neuropathy models.The Journal of clinical investigation · 2025Article
- Human sensory neurons exhibit cell-type-specific, pain-associated differences in intrinsic excitability and expression ofbioRxiv : the preprint server for biology · 2025Article
- Electrophysiological Analyses of Human Dorsal Root Ganglia and Human Induced Pluripotent Stem Cell-derived Sensory Neurons From Male and Female Donors.The journal of pain · 2024Article
- Metabotropic glutamate receptors (mGluRs) in epileptogenesis: an update on abnormal mGluRs signaling and its therapeutic implications.Neural regeneration research · 2024Review
- Sex-differences in prostaglandin signaling: a semi-systematic review and characterization of PTGDS expression in human sensory neurons.Scientific reports · 2023Review
- RNA profiling of human dorsal root ganglia reveals sex differences in mechanisms promoting neuropathic pain.Brain : a journal of neurology · 2023Article
- Metabotropic glutamate receptor function and regulation of sleep-wake cycles.International review of neurobiology · 2023Article
- Review
- Sensory neuron dysfunction in orthotopic mouse models of colon cancer.Journal of neuroinflammation · 2022Article
- Innovations and advances in modelling and measuring pain in animals.Nature reviews. Neuroscience · 2022Review
- Glutamatergic system components as potential biomarkers and therapeutic targets in cancer in non-neural organs.Frontiers in endocrinology · 2022Review
- Article
- Studying human nociceptors: from fundamentals to clinic.Brain : a journal of neurology · 2021Review
- Usefulness of the measurement of neurite outgrowth of primary sensory neurons to study cancer-related painful complications.Biochemical pharmacology · 2021Article
- Review
- A ligand-receptor interactome platform for discovery of pain mechanisms and therapeutic targets.Science signaling · 2021Article
- Cannabinoid Receptor 1 Expression in Human Dorsal Root Ganglia and CB13-Induced Bidirectional Modulation of Sensory Neuron Activity.Frontiers in pain research (Lausanne, Switzerland) · 2021Article
- The Role of Glutamate in Language and Language Disorders - Evidence from ERP and Pharmacologic Studies.Neuroscience and biobehavioral reviews · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
We introduce a strategy for preclinical research wherein promising targets for analgesia are tested in rodent and subsequently validated in human sensory neurons. We evaluate group II metabotropic glutamate receptors, the activation of which is efficacious in rodent models of pain. Immunohistochemical analysis showed positive immunoreactivity for mGlu2 in rodent dorsal root ganglia (DRG), peripheral fibers in skin, and central labeling in the spinal dorsal horn. We also found mGlu2-positive immunoreactivity in human neonatal and adult DRG. RNA-seq analysis of mouse and human DRG revealed a comparative expression profile between species for group II mGluRs and for opioid receptors. In rodent sensory neurons under basal conditions, activation of group II mGluRs with a selective group II agonist produced no changes to membrane excitability. However, membrane hyperexcitability in sensory neurons exposed to the inflammatory mediator prostaglandin E2 (PGE2) was prevented by (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC). In human sensory neurons from donors without a history of chronic pain, we show that PGE2 produced hyperexcitability that was similarly blocked by group II mGluR activation. These results reveal a mechanism for peripheral analgesia likely shared by mice and humans and demonstrate a translational research strategy to improve preclinical validation of novel analgesics using cultured human sensory neurons.
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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.