Efficacy of ketamine in relieving neuropathic pain: a systematic review and meta-analysis of animal studies.

Abstract

ABSTRACT:

In humans, proof of long-term efficacy of ketamine treatment in neuropathic pain is lacking. To improve our understanding of ketamine behavior under various administration conditions, we performed a systematic review and meta-analyses of controlled studies on the efficacy of ketamine in mice and rats with a disease model of nerve injury on relief of allodynia. Searches in PubMed and EMBASE identified 31 unique studies. Four meta-analyses were conducted. The first analysis included 19 comparisons on a single ketamine dose and measurement of effect within 3 hours of dosing and showed an appreciable effect (standardized mean difference 1.6, 95% confidence interval 1.1-2.1). Subgroup analyses showed no effect of species, administration route, or dose. A single administration was insufficient to sustain relief of allodynia at 24 or 72 hours after dosing, as observed in our second analysis (7 comparisons) with similar effects in ketamine-treated and control animals. Chronic ketamine administration (9 comparisons) caused profound relief of allodynia when tested during ketamine exposure (effect size 5.1, 3.7-6.5). The final analysis (6 comparisons) showed that chronic administration caused a slow loss of relief of allodynia with 70% loss of effect 24 days after end of treatment. No subgroups analyses were possible in the last 3 meta-analyses due to small group sizes. These results indicate long-term ketamine anti-allodynic effects after chronic exposure (>3 days) but not after a single administration. Given several limitations, extrapolation of the animal data to the human condition is tenuous.

• Authors: Monique van Velzen, Jack D C Dahan, Eveline L A van Dorp, Jeffrey S Mogil, Carlijn R Hooijmans, Albert Dahan
• Journal: Pain (Pain) Vol. 162 Issue 9 Pg. 2320-2330 (09 01 2021) ISSN: 1872-6623 [Electronic] United States
• PMID: 33790195 (Publication Type: Journal Article, Meta-Analysis, Systematic Review)
• Copyright: Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.

Chemical References

• Ketamine

Topics

• Animals
• Hyperalgesia (drug therapy)
• Ketamine (therapeutic use)
• Mice
• Neuralgia (drug therapy)
• Rats