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Over the last several years, significant progress has been made in our understanding of interactions between the N-methyl-d-aspartate (NMDA) and opioid receptors. Such interactions have been demonstrated at two distinct sites: (1) modulation of NMDA receptor-mediated electrophysiological events by opioids; and (2) intracellular events involving interactions between NMDA and opioid receptors. Furthermore, a considerable number of studies have shown the involvement of such interactions in neural mechanisms of nociceptive transmission, antinociception in acute and chronic pain states, opioid tolerance/dependence, and neuroplasticity. Importantly, emerging evidence indicates that activation of NMDA receptors may differentially modulate functions mediated by distinct opioid receptor subtypes, namely μ, δ, and κ receptors. These studies have greatly enriched our knowledge regarding both NMDA and opioid …