RT Journal Article
SR Electronic
T1 NMDA receptor antagonists and pain relief
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP e1652
OP e1662
DO 10.1212/WNL.0000000000007238
VO 92
IS 14
A1 Thompson, Trevor
A1 Whiter, Fiona
A1 Gallop, Katy
A1 Veronese, Nicola
A1 Solmi, Marco
A1 Newton, Paul
A1 Stubbs, Brendon
YR 2019
UL http://n.neurology.org/content/92/14/e1652.abstract
AB Objective We conducted a meta-analysis of controlled trials that used experimental models of acute pain and hyperalgesia to examine the analgesic effects of NMDA receptor (NMDAR) antagonists.Methods Six major databases were systematically searched (to March 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.Results Searches identified 70 eligible trials (n = 1,069). Meta-analysis found that low-dose ketamine (<1 mg/kg) produced a decrease in hyperalgesic area (standardized mean difference 0.54, 95% confidence interval [CI] 0.34, 0.74, p < 0.001) and a 1.2-point decrease (95% CI 0.88, 1.44, p < 0.001) 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 to high variability in effect size was observed and mild side effects (e.g., sedation, sensory disturbance) were common. No effects of dextromethorphan were found.Conclusions Findings provide robust evidence for analgesic and antihyperalgesic 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.CI=confidence interval; NMDAR=NMDA receptor; RVE=robust variance estimation; SMD=standardized mean difference