A pro-nociceptive role of neuromedin U in adult mice.
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 microM) 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 microM, 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 microl) 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.
Cao
Chang Qing
CQ
AstraZeneca R&D Montreal, 7171 Frederick-Banting, St-Laurent, Montreal, Quebec, Canada H4S 1Z9.
Yu
Xiao Hong
XH
Dray
Andy
A
Filosa
Angelo
A
Perkins
Martin N
MN
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D009479:Neuropeptides / Q000633:toxicity*; D010146:Pain / Q000139:chemically induced* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D020671:Posterior Horn Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000819:agonists / Q000502:physiology
D008565:Membrane Proteins; D009479:Neuropeptides; D017981:Receptors, Neurotransmitter; C082444:neuromedin U receptor; C056900:neuromedin U