A pro-nociceptive role of neuromedin U in adult mice

Although the neuropeptide neuromedin U (NMU) was first isolated from he 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 muM) 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 muM, 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 nmnol/10 mul) 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. (C) 2003 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.