The present study examined the effects of cocaine-regulated and amphetamine-regulated transcript peptide (CARTp) fragment 55–102, on N-methyl-D-aspartate (NMDA)-mediated nociceptive transmission in vivo and in vitro. In-vivo experiments were conducted in Sprague–Dawley rats to evaluate the effects of CARTp on thermal hyperalgesia induced by NMDA or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Intrathecal NMDA (1, 2, 4 nmol) or AMPA (0.5, 1, 2 nmol) dose-dependently decreased the tail-flick latency. Intrathecal CARTp was without effect on the tail-flick latency. Interestingly, it significantly enhanced NMDA-induced, but not AMPA-induced, nociceptive effects. The in-vitro effects of CARTp on NMDA-induced or AMPA-induced depolarizations in substantia gelatinosa neurons were studied in rat spinal cord slices. CARTp (100, 300 nM), which caused no significant change of membrane potentials, increased the amplitude of NMDA-induced depolarizations in substantia gelatinosa neurons with little effect on AMPA-induced depolarizations. The present study demonstrates that exogenously applied CARTp selectively facilitates NMDA receptor-mediated nociceptive transmission.