Antagonism of the NMDA receptor has no primary analgesic effect but rather it has opioid-sparing, opioid tolerance-reversing, and anti-hyperalgesic/neuropathic effects. Ketamine, in addition to being an NMDA antagonist, interacts with opioid, noradrenergic, and muscarinic receptors and voltage-sensitive calcium channels, thus it has true analgesic properties in addition to the NMDA class effects. Ketamine use improves pain scores and has an opioid sparing effect of up to 50% though there are equivocal benefits in terms of a reduction of opioid-induced side effects.
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