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N-Methyl-D-aspartate receptor antagonists for the prevention of chronic postsurgical pain: a narrative review
  1. Jeffrey Jon Mojica,
  2. Grace Eddy and
  3. Eric S Schwenk
  1. Anesthesiology and Perioperative Medicine, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania, USA
  1. Correspondence to Dr Jeffrey Jon Mojica; jeffrey.mojica{at}jefferson.edu

Abstract

The N-methyl-D-aspartate receptor (NMDAR) has been linked to the development of chronic postsurgical pain (CPSP), defined as pain after surgery that does not resolve by 3 months. Once the combination of a painful stimulus and glutamate binding activates the NMDAR, calcium influx triggers signaling cascades that lead to processes like central sensitization and CPSP. Three of the most widely studied perioperative NMDAR antagonists include ketamine, magnesium, and methadone, with ketamine having garnered the greatest amount of attention. While multiple studies have found improved analgesia in the acute postoperative period, fewer studies have focused on long-term outcomes and those that have are often underpowered for CPSP or have not included those patients at highest risk. Existing meta-analyses of ketamine for CPSP are inconsistent in their findings, and studies of magnesium and methadone are even more limited. Overall, the evidence supporting NMDAR antagonists for CPSP is weak and we recommend that future studies focus on high-risk patients and potentially include combinations of NMDAR antagonists administered together for the longest duration feasible. The results of ongoing trials could have a major influence on the overall direction of the evidence supporting NMDAR antagonists in preventing CPSP.

  • Pain, Postoperative
  • Acute Pain
  • Analgesia
  • Pharmacology
  • Public Health

Data availability statement

There are no data in this work.

https://doi.org/10.1136/rapm-2024-105612

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    Data availability statement

    There are no data in this work.

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    Footnotes

    • X @ESchwenkMD

    • Contributors JJM and ESS helped perform the literature search, screen articles, and prepare the manuscript. GE helped create the figures and prepare the manuscript. ESS is the guarantor.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.