NMDA-receptor antagonists and opioid receptor interactions as related to analgesia and tolerance
Price DD, Mayer DJ, Mao J, Caruso FS.
Department of Oral and Maxillofacial Surgery,
University of Florida, USA.
J Pain Symptom Manage 2000 Jan; 19(1 Suppl):S7-11


A model proposing that N-methyl-D-aspartate (NMDA) receptor and opioid receptor mechanisms overlap and interact within the same dorsal horn nociceptive neurons makes several predictions. First, hyperalgesia should be associated with opioid tolerance. Second, both hyperalgesia and tolerance to opioid-analgesia should be blocked by an NMDA-receptor antagonist. Results from our laboratory and others support these predictions and point to several clinical implications. One is that, in addition to preventing tolerance and dependence, combining NMDA-receptor antagonists with both opioid and nonopioid analgesics may increase their analgesic potency. Preclinical animal studies demonstrate these advantages and underscore the practicality of the combined administration of nontoxic NMDA-receptor antagonists with various types of analgesic drugs.
Zero tolerance?
NMDA antagonists
Pain and the NMDA receptor
NMDA antagonists for drug users
Neuropathic pain and NMDA antagonists
NMDA antagonists against morphine tolerance
NMDA receptors and opiate-induced neural plasticity

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