ArticleNeuropharmacology2014
Gabapentin increases extracellular glutamatergic level in the locus coeruleus via astroglial glutamate transporter-dependent mechanisms.
Article in Neuropharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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.
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
25 citing papers in PubMed, 56 citations in OpenAlex.
- Pilot randomized placebo-controlled clinical trial of high-dose gabapentin for alcohol use disorder.Alcoholism, clinical and experimental research · 2021Trial
- Efficacy of Gabapentin for the Treatment of Alcohol Use Disorder in Patients With Alcohol Withdrawal Symptoms: A Randomized Clinical Trial.JAMA internal medicine · 2020Trial
- Pregabalin enhances the proliferative potential of pancreatic cancer in vitro but not in mice with pancreatic cancer.BMC pharmacology & toxicology · 2026Article
- Multifaceted Astrocyte-Neuron Cross-Talk in Neuropathic Pain: Potential Mechanisms and Functional Implications.Journal of pain research · 2026Review
- Calcium Channel αPain and therapy · 2025Review
- Duloxetine deteriorates prefrontal noradrenergic pain facilitation, but reduces locus coeruleus activity to restore endogenous analgesia in chronic neuropathic pain state.Scientific reports · 2025Article
- Review
- Neuropathic pain in cats: Mechanisms and multimodal management.Journal of feline medicine and surgery · 2024Review
- Gabapentin: Clinical Use and Pharmacokinetics in Dogs, Cats, and Horses.Animals : an open access journal from MDPI · 2023Review
- Glial Glutamate Transporter Modulation Prevents Development of Complete Freund's Adjuvant-Induced Hyperalgesia and Allodynia in Mice.Brain sciences · 2023Article
- Article
- Astrocytes as a target for therapeutic strategies in epilepsy: current insights.Frontiers in molecular neuroscience · 2023Review
- Adolescent intermittent ethanol exposure reduces astrocyte-synaptic proximity in the adult medial prefrontal cortex in rats: Reversal by gabapentin.Addiction neuroscience · 2022Article
- Altered expression of vesicular glutamate transporter-2 and cleaved caspase-3 in the locus coeruleus of nerve-injured rats.Frontiers in molecular neuroscience · 2022Article
- Effects of adolescent intermittent ethanol on hippocampal expression of glutamate homeostasis and astrocyte-neuronal tethering proteins in male and female rats.Journal of neuroscience research · 2021Article
- Gabapentin reduces painful bladder hypersensitivity in rats with lipopolysaccharide-induced chronic cystitis.Pharmacology research & perspectives · 2021Article
- Gabapentinoids: pharmacokinetics, pharmacodynamics and considerations for clinical practice.British journal of pain · 2020Article
- Strategies to Treat Chronic Pain and Strengthen Impaired Descending Noradrenergic Inhibitory System.International journal of molecular sciences · 2019Review
- Blockade of α2-adrenergic or metabotropic glutamate receptors induces glutamate release in the locus coeruleus to activate descending inhibition in rats with chronic neuropathic hypersensitivity.Neuroscience letters · 2018Article
- The noradrenergic locus coeruleus as a chronic pain generator.Journal of neuroscience research · 2017Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Gabapentin has shown to be effective in animals and humans with acute postoperative and chronic pain. Yet the mechanisms by which gabapentin reduces pain have not been fully addressed. The current study performed in vivo microdialysis in the locus coeruleus (LC) in normal and spinal nerve ligated (SNL) rats to examine the effect of gabapentin on extracellular glutamate concentration and its mechanisms of action with focus on presynaptic GABA-B receptors, astroglial glutamate transporter-1 (GLT-1), and interactions with α2δ subunits of voltage-gated Ca(2+) channels and endogenous noradrenaline. Basal extracellular concentration and tissue content of glutamate in the LC were greater in SNL rats than normal ones. Intravenously administered and LC-perfused gabapentin increased extracellular glutamate concentration in the LC. The net amount of glutamate increased by gabapentin is larger in SNL rats compared with normal ones, although the percentage increases from the baseline did not differ. The gabapentin-related α2δ ligand pregabalin increased extracellular glutamate concentration in the LC, whereas another α2δ ligand, 3-exo-aminobicyclo [2.2.1] heptane-2-exo-carboxylic acid (ABHCA), did not. Selective blockade by the dihydrokainic acid or knock-down of GLT-1 by the small interfering RNA abolished the gabapentin-induced glutamate increase in the LC, whereas blockade of GABA-B receptors by the CGP-35348 and depletion of noradrenalin by the dopamine-β-hydroxylase antibody conjugated to saporin did not. These results suggest that gabapentin induces glutamate release from astrocytes in the LC via GLT-1-dependent mechanisms to stimulate descending inhibition. The present study also demonstrates that this target of gabapentin in astrocytes does not require interaction with α2δ subunits in 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.