ArticlePain2015
The lidocaine metabolite N-ethylglycine has antinociceptive effects in experimental inflammatory and neuropathic pain.
Article in Pain, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Lidocaine for postoperative pain after cardiac surgery: a systematic review.Journal of cardiothoracic surgery · 2021Pooled it
- Trial
- Modulation of glycine transporters as a novel therapeutic strategy in neuropsychiatry.Psychopharmacology · 2026Review
- Glycine transport inhibitors for the treatment of chronic pain conditions: the time is ripe for clinical evaluation!Frontiers in molecular neuroscience · 2026Article
- Interactions Involving Glycine and Other Amino Acid Neurotransmitters: Focus on Transporter-Mediated Regulation of Release and Glycine-Glutamate Crosstalk.Biomedicines · 2024Review
- A single infusion of intravenous lidocaine for primary headaches and trigeminal neuralgia: a retrospective analysis.Frontiers in neurology · 2023Article
- Synergistic Control of Transmitter Turnover at Glycinergic Synapses by GlyT1, GlyT2, and ASC-1.International journal of molecular sciences · 2022Review
- Bupivacaine reduces GlyT1 expression by potentiating the p-AMPKα/BDNF signalling pathway in spinal astrocytes of rats.Scientific reports · 2022Article
- Lidocaine Ameliorates Diabetic Peripheral Neuropathy in Streptozotocin-Induced Diabetic Rats through Modulating the c-Jun Signaling Pathway.Contrast media & molecular imaging · 2022Article
- Glycinergic Modulation of Pain in Behavioral Animal Models.Frontiers in pharmacology · 2022Review
- Intravenous Lidocaine and Ketamine Infusions for Headache Disorders: A Retrospective Cohort Study.Frontiers in neurology · 2022Article
- Structural diversity in the coordination compounds of cobalt, nickel and copper withRSC advances · 2021Article
- Inhibition of Glycine Re-Uptake: A Potential Approach for Treating Pain by Augmenting Glycine-Mediated Spinal Neurotransmission and Blunting Central Nociceptive Signaling.Biomolecules · 2021Review
- Topical Treatments and Their Molecular/Cellular Mechanisms in Patients with Peripheral Neuropathic Pain-Narrative Review.Pharmaceutics · 2021Review
- Modulation of Glycinergic Neurotransmission may Contribute to the Analgesic Effects of Propacetamol.Biomolecules · 2021Article
- Effect of two-week continuous epidural administration of 2% lidocaine on mechanical allodynia induced by spinal nerve ligation in rats.Anesthesia and pain medicine · 2020Article
- Reviewing the case for compromised spinal inhibition in neuropathic pain.Journal of neural transmission (Vienna, Austria : 1996) · 2020Review
- Review
- Fermentative Production ofFrontiers in bioengineering and biotechnology · 2019Article
- Intravenous infusion of lidocaine enhances the efficacy of conventional treatment of postherpetic neuralgia.Journal of pain research · 2019Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Glycine transporter 1 (GlyT1) plays a crucial role in regulating extracellular glycine concentrations and might thereby constitute a new drug target for the modulation of glycinergic inhibition in pain signaling. Consistent with this view, inhibition of GlyT1 has been found to induce antinociceptive effects in various animal pain models. We have shown previously that the lidocaine metabolite N-ethylglycine (EG) reduces GlyT1-dependent glycine uptake by functioning as an artificial substrate for this transporter. Here, we show that EG is specific for GlyT1 and that in rodent models of inflammatory and neuropathic pain, systemic treatment with EG results in an efficient amelioration of hyperalgesia and allodynia without affecting acute pain. There was no effect on motor coordination or the development of inflammatory edema. No adverse neurological effects were observed after repeated high-dose application of EG. EG concentrations both in blood and spinal fluid correlated with an increase of glycine concentration in spinal fluid. The time courses of the EG and glycine concentrations corresponded well with the antinociceptive effect. Additionally, we found that EG reduced the increase in neuronal firing of wide-dynamic-range neurons caused by inflammatory pain induction. These findings suggest that systemically applied lidocaine exerts antihyperalgesic effects through its metabolite EG in vivo, by enhancing spinal inhibition of pain processing through GlyT1 modulation and subsequent increase of glycine concentrations at glycinergic inhibitory synapses. EG and other substrates of GlyT1, therefore, may be a useful therapeutic agent in chronic pain states involving spinal disinhibition.
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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.