Involvement of glutamatergic receptors in the nucleus cuneiformis in modulating morphine-induced antinociception in rats

Abstract The nucleus cuneiformis (CnF), located just ventrolateral to the periaqueductal gray, is part of the descending pain modulatory system. Neurons in the CnF project to medullary nucleus raphe magnus (NRM), which plays an important role on pain modulation. In this study, we investigated the effect of microinjection of the non-competitive NMDA receptor antagonist MK-801, the competitive NMDA receptor antagonist AP-7, and the kainate/AMPA receptor antagonist DNQX, alone or in combination with morphine into the nucleus cuneiformis on morphine-induced analgesia to understand the role of glutamatergic receptors in the modulating activity of morphine. Antinociception was assessed with the tail-flick test. Morphine (10, 20, 40 μg in 0.5 μl saline) had an antinociceptive effect, increasing tail-flick latency in a dose-dependent manner. Microinjection of MK-801 (10 μg/0.5 μl saline) and AP7 (3 μg/0.5 μl saline) prior to morphine microinjection (10 μg/0.5 μl saline) attenuated the antinociceptive effects of morphine, whereas DNQX (0.5 μg/0.5 μl saline) showed a partial antinociceptive effect and potentiated the analgesic effect of morphine. These results indicated that the NMDA receptor partially potentiates the antinociceptive effect of morphine. Our results suggest that NMDA but not non-NMDA receptors are involved in the antinociception produced by morphine in the CnF. The non-NMDA receptors in this area may have a facilitatory effect on nociceptive transmission. The fact that morphine’s effect was potentiated by NMDA receptor suggests that projection neurons within the CnF are under tonic, glutamatergic input and when the influence of this input is blocked, the descending inhibitory system is inactivated.