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

• Published in: Pain (Amsterdam) Vol. 162; no. 9; pp. 2320 - 2330
• Main Authors: Velzen, Monique van, Dahan, Jack D C, van Dorp, Eveline L A, Mogil, Jeffrey S, Hooijmans, Carlijn R, Dahan, Albert
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer 01.09.2021
• Subjects: Animals; Hyperalgesia - drug therapy; Ketamine - therapeutic use; Mice; Neuralgia - drug therapy; Rats; Systematic Review and Meta-Analysis
• DOI: 10.1097/j.pain.0000000000002231
• ISSN: 0304-3959

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.