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NMDA receptor antagonists and pain relief: A meta-analysis of experimental trials

NMDA receptor antagonists and pain relief: A meta-analysis of experimental trials

Thompson, Trevor ORCID: 0000-0001-9880-782X, Whiter, Fiona, Gallop, Katy, Veronese, Nicola, Solmi, Marco, Newton, Paul ORCID: 0000-0002-8525-6763 and Stubbs, Brendon (2019) NMDA receptor antagonists and pain relief: A meta-analysis of experimental trials. Neurology, 92 (14). ISSN 0028-3878 (Print), 1526-632X (Online) (doi:

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We conducted a meta-analysis of controlled trials that used experimental models of acute pain and hyperalgesia to examine the analgesic effects of N-methyl-D-aspartate receptor (NMDAR) antagonists.

Six major databases were systematically searched (to 03/2018) for studies using human evoked pain models to compare NMDAR antagonists with no-intervention controls. Pain outcome data were analyzed with random-effects meta-analysis.

Searches identified 70 eligible trials (N=1069). Meta-analysis found that low-dose ketamine (<1 mg/kg) produced a decrease in the size of hyperalgesic area (Standardized Mean Difference=0.54, CI95[0.34, 0.74], p<.001), and a 1.2-point decrease (CI95[0.88, 1.44], p<.001) in pain ratings from 4.6 to 3.4 on a 0-10 scale (a 26% reduction). Similar analgesia was observed for acute and hyperalgesic models and was constant across the dosing range (0.03-1.00 mg/kg). Moderate-high variability in effect size was observed and mild side effects (e.g. sedation, sensory disturbance) were common. No effects of dextromethorphan were found.

Findings provide robust evidence for analgesic and anti-hyperalgesic effects of ketamine, supporting its utility for acute and chronic pain management. However, pain relief was modest, suggesting ketamine may potentially be most useful when opioids are contraindicated, rapid analgesia is required or for pain resistant to conventional medication.

Item Type: Article
Uncontrolled Keywords: pain, NMDA, ketamine, dextromethorphan, analgesia, review, meta-analysis
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Faculty / Department / Research Group: Faculty of Education & Health
Faculty of Education & Health > Applied Psychology Research Group
Faculty of Education & Health > Department of Adult Nursing & Paramedic Science
Faculty of Education & Health > Department of Psychology, Social Work & Counselling
Last Modified: 16 May 2019 11:42
Selected for GREAT 2016: None
Selected for GREAT 2017: None
Selected for GREAT 2018: None
Selected for GREAT 2019: GREAT 1

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