ArticlePain2016
Gabapentin loses efficacy over time after nerve injury in rats: role of glutamate transporter-1 in the locus coeruleus.
Article in Pain, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 36 citations in OpenAlex.
- Spared Nerve Injury Induces Long-Term and Brain Region-Specific Changes in Oligodendrocyte Density in Mice.European journal of pain (London, England) · 2026Article
- Spared nerve injury induces long-term and brain region-specific changes in oligodendrocyte density in mice.bioRxiv : the preprint server for biology · 2025Article
- Monosynaptic ventral tegmental area glutamate projections to the locus coeruleus enhance aversive processing.bioRxiv : the preprint server for biology · 2024Article
- Peripheral direct current reduces naturally evoked nociceptive activity at the spinal cord in rodent models of pain.Journal of neural engineering · 2024Article
- Glial Glutamate Transporter Modulation Prevents Development of Complete Freund's Adjuvant-Induced Hyperalgesia and Allodynia in Mice.Brain sciences · 2023Article
- Article
- Gabapentin-Friend or foe?Pain practice : the official journal of World Institute of Pain · 2023Review
- Temporal model for central sensitization: A hypothesis for mechanism and treatment using systemic manual therapy, a focused review.MethodsX · 2023Review
- Opioid signaling and design of analgesics.Progress in molecular biology and translational science · 2023Review
- Glutamatergic systems in neuropathic pain and emerging non-opioid therapies.Pharmacological research · 2022Review
- Effectiveness of Duloxetine for Postsurgical Chronic Neuropathic Disorders after Spine and Spinal Cord Surgery.Asian spine journal · 2021Article
- Gabapentinoids: pharmacokinetics, pharmacodynamics and considerations for clinical practice.British journal of pain · 2020Article
- High-Voltage-Activated Calcium Channel in the Afferent Pain Pathway: An Important Target of Pain Therapies.Neuroscience bulletin · 2019Article
- Peripheral nerve injury in rats induces alternations in choice behavior associated with food reinforcement.The journal of physiological sciences : JPS · 2019Article
- Strategies to Treat Chronic Pain and Strengthen Impaired Descending Noradrenergic Inhibitory System.International journal of molecular sciences · 2019Review
- Repeated Sigma-1 Receptor Antagonist MR309 Administration Modulates Central Neuropathic Pain Development After Spinal Cord Injury in Mice.Frontiers in pharmacology · 2019Article
- The noradrenergic locus coeruleus as a chronic pain generator.Journal of neuroscience research · 2017Review
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Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
Despite being one of the first-choice analgesics for chronic neuropathic pain, gabapentin sometimes fails to provide analgesia, but the mechanisms for this lack of efficacy is unclear. Rats with nerve injury including L5-L6 spinal nerve ligation (SNL) respond uniformly and well to gabapentin, but many of these studies are performed within just a few weeks of injury, questioning their relevance to chronic neuropathic pain. In this study, intraperitoneal gabapentin showed a time-dependently reduction in antihypersensitivity after SNL, associated with downregulation of astroglial glutamate transporter-1 (GLT-1) in the locus coeruleus (LC). Consistently, SNL also time-dependently increased basal but masked gabapentin-induced noradrenergic neuronal activity in the LC. In rats 2 weeks after SNL, knock-down of GLT-1 in the LC reduced the antihypersensitivity effect of gabapentin. In rats 8 weeks after SNL, increasing GLT-1 expression by histone deacetylase inhibitor valproate restored the antihypersensitivity effect of gabapentin, associated with restored gabapentin-induced noradrenergic neuronal activity in the LC and subsequent spinal noradrenaline release. Knock-down of GLT-1 in the LC reversed the effect of valproate to restore gabapentin-induced antihypersensitivity. In addition, the antihypersensitivity effect of the intrathecal α2-adrenoceptor agonist clonidine also decreased with time after SNL injury. These results suggest that downregulation of GLT-1 in the LC and reduced spinal noradrenergic inhibition contribute to impaired analgesic efficacy from gabapentin in chronic neuropathic pain and that valproate can rescue this impaired efficacy.
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What OpenQuestion holds
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.