Co-localization of mu opioid receptor and N-methyl-D-aspartate receptor in the trigeminal dorsal horn

Antagonists acting at the N-methyl-D-aspartate (NMDA) receptor can block the development of tolerance to the analgesic effects of μ opioid receptor (MOR) ligands, such as morphine, and can also enhance the analgesic efficacy of opioids. These findings have led to the hypothesis that interactions between NMDA receptor and MOR ligands may be due to the co-localization of these receptors on neurons in the dorsal horn. We used dual immunogold and immunoperoxidase immunocytochemistry for MOR1 and NMDAR1 to determine the degree of co-localization of these receptors in neurons of the trigeminal dorsal horn. By use of electron microscopy, we found that both receptors were primarily located in dendrites and to a lesser extent in perikarya, axons, axon terminals, and glia. With regard to the degree of co-localization in dendrites, 63% of MOR1-labeled dendrites also contained NMDAR1, whereas 61% of NMDAR1-labeled dendrites also contained MOR1. Most of the dual-labeled profiles (94%) were classified as dendrites, with the remainder being axons, axon terminals, or perikarya. These results suggest that direct interactions between MOR and NMDA receptor ligands are likely mediated through shared dendritic targets in the dorsal horn. Less frequently, we found evidence for modulation of afferents to MOR-containing neurons through presynaptic NMDA receptors.