Although the neuropeptide neuromedin U (NMU) was first isolated from the spinal cord, its actions in this site are unknown. The recent identification of the NMU receptor subtype 2 (NMU2R) in the spinal cord has increased the interest in investigating the role of NMU in this part of the central nervous system. Here, we report a novel function for NMU in spinal nociception in the mouse. Systemic perfusion of NMU (rat, NMU-23) dose-dependently (0.2, 0.5, 1, and 2.5 μM) potentiated both the background activity and noxious pinch-evoked response of nociceptive or wide dynamic range, but not non-nociceptive, dorsal horn neurons. At 2.5 μM, NMU-23 increased the total background activity from 154±34 to 1374±260 spikes/160 s (P< 0.005, n= 28) and increased the evoked nociceptive response by 185±50%(P< 0.01, n= 13). Intrathecal administration of NMU-23 (0.4, 1.1, and 3.8 nmol/10 μl) dose-dependently decreased thermal withdrawal latencies and produced a morphine-sensitive behavioral response. These electrophysiological and behavioral results suggest that NMU may be a novel physiological regulator in spinal nociceptive transmission and processing.