N-Methyl-D-aspartate receptor antagonists for the prevention of chronic postsurgical pain: a narrative review.
Regional anesthesia and pain medicine February 5, 2025 Jeffrey Jon Mojica, Grace Eddy, Eric S Schwenk 5 citations
The N-methyl-D-aspartate receptor (NMDAR) is linked to chronic postsurgical pain (CPSP), pain persisting beyond three months after surgery. Activation of NMDAR by painful stimuli and glutamate triggers calcium influx and signaling cascades leading to central sensitization and CPSP. The most studied perioperative NMDAR antagonists—ketamine, magnesium, and methadone—show improved acute postoperative analgesia, but evidence for preventing CPSP is weak. Few studies examine long-term outcomes, and those that do are often underpowered or exclude high-risk patients. Meta-analyses of ketamine for CPSP yield inconsistent findings; data on magnesium and methadone are even more limited. Future research should focus on high-risk patients and combinations of antagonists given for the longest feasible duration.