ArticleBritish journal of pharmacology2015
Ketamine coadministration attenuates morphine tolerance and leads to increased brain concentrations of both drugs in the rat.
Article in British journal of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03959852 (A Combination Study With Sub-Dissociative Ketamine and Fentanyl to Treat Moderate to Severe Pain in the Emergency Department), which is not on this map. Cited by 22 papers, 3 of them syntheses 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.
A Combination Study With Sub-Dissociative Ketamine and Fentanyl to Treat Moderate to Severe Pain in the Emergency Department
Who cites it
22 citing papers in PubMed, 3 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- Ketamine and other NMDA receptor antagonists for chronic pain.The Cochrane database of systematic reviews · 2025Pooled it
- Perioperative intravenous ketamine for acute postoperative pain in adults.The Cochrane database of systematic reviews · 2018Pooled it
- Ketamine as an adjuvant to opioids for cancer pain.The Cochrane database of systematic reviews · 2017Pooled it
- Chronic Opioid Therapy Modifies QST Changes After Ketamine Infusion in Chronic Pain Patients.The journal of pain · 2017Trial
- Increase of the AMPA-evoked response of pyramidal neurons in the rat medial prefrontal cortex following acute administration of ketamine and S-ketamine, but not R-ketamine.The international journal of neuropsychopharmacology · 2026Article
- The Efficacy of Ketamine for Acute and Chronic Pain in Patients with Cancer: A Systematic Review of Randomized Controlled Trials.Healthcare (Basel, Switzerland) · 2024Review
- Anaesthesia in Veterinary Oncology: The Effects of Surgery, Volatile and Intravenous Anaesthetics on the Immune System and Tumour Spread.Animals : an open access journal from MDPI · 2023Review
- Hydrocodone, Oxycodone, and Morphine Metabolism and Drug-Drug Interactions.The Journal of pharmacology and experimental therapeutics · 2023Review
- Narrative Review: Low-Dose Ketamine for Pain Management.Journal of clinical medicine · 2023Review
- Determination of Diffusion Kinetics of Ketamine in Brain Tissue: Implications forFrontiers in neuroscience · 2021Article
- Neuroinflammation, Pain and Depression: An Overview of the Main Findings.Frontiers in psychology · 2020Review
- KEA-1010, a ketamine ester analogue, retains analgesic and sedative potency but is devoid of Psychomimetic effects.BMC pharmacology & toxicology · 2019Article
- [Ketamine in the therapy of chronic pain and depression].Wiener medizinische Wochenschrift (1946) · 2019Review
- Ketamine Pharmacokinetics and Pharmacodynamics Are Altered by P-Glycoprotein and Breast Cancer Resistance Protein Efflux Transporters in Mice.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Chronic Pain From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists.Regional anesthesia and pain medicine · 2018Review
- Additive and subadditive antiallodynic interactions between μ-opioid agonists and N-methyl D-aspartate antagonists in male rhesus monkeys.Behavioural pharmacology · 2018Article
- Chronic morphine exposure potentiates p-glycoprotein trafficking from nuclear reservoirs in cortical rat brain microvessels.PloS one · 2018Article
- Article
- BK channels in microglia are required for morphine-induced hyperalgesia.Nature communications · 2016Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe effects of ketamine in attenuating morphine tolerance have been suggested to result from a pharmacodynamic interaction. We studied whether ketamine might increase brain morphine concentrations in acute coadministration, in morphine tolerance and morphine withdrawal. EXPERIMENTAL APPROACH: Morphine minipumps (6 mg·day(-1) ) induced tolerance during 5 days in Sprague-Dawley rats, after which s.c. ketamine (10 mg·kg(-1) ) was administered. Tail flick, hot plate and rotarod tests were used for behavioural testing. Serum levels and whole tissue brain and liver concentrations of morphine, morphine-3-glucuronide, ketamine and norketamine were measured using HPLC-tandem mass spectrometry. KEY
resultsIn morphine-naïve rats, ketamine caused no antinociception whereas in morphine-tolerant rats there was significant antinociception (57% maximum possible effect in the tail flick test 90 min after administration) lasting up to 150 min. In the brain of morphine-tolerant ketamine-treated rats, the morphine, ketamine and norketamine concentrations were 2.1-, 1.4- and 3.4-fold, respectively, compared with the rats treated with morphine or ketamine only. In the liver of morphine-tolerant ketamine-treated rats, ketamine concentration was sixfold compared with morphine-naïve rats. After a 2 day morphine withdrawal period, smaller but parallel concentration changes were observed. In acute coadministration, ketamine increased the brain morphine concentration by 20%, but no increase in ketamine concentrations or increased antinociception was observed. CONCLUSIONS AND IMPLICATIONS: The ability of ketamine to induce antinociception in rats made tolerant to morphine may also be due to increased brain concentrations of morphine, ketamine and norketamine. The relevance of these findings needs to be assessed in humans.
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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.