NMDA-receptor antagonists and opioid receptor interactions as related to analgesia and tolerance

A model proposing that N-methyl-D-aspartate (NMDA) receptor and opioid rece ptor mechanisms overlap and interact within the same dorsal horn nociceptiv e neurons makes several predictions. First, hyperalgesia should be associat ed with opioid tolerance. Second, both hyperalgesia and tolerance to opioid -analgesia should be blocked fry an NMDA-receptor antagonist. Results from our laboratory and others support these predictions and point to several cl inical implications. One is that, in addition to preventing tolerance and d ependence, combining NMDA-receptor antagonists with both opioid and nonopio id analgesics may increase their analgesic potency. Preclinical animal stud ies demonstrate these advantages and underscore the practicality of the com bined administration of nontoxic NMDA-receptor antagonists with various typ es of analgesic drugs. J Pain Symptom Manage 2000;S7-S11. (C) U.S. Cancer P ain Relief Committee, 2000.