The neuropeptide neuromedin U (NMU) has been shown to have significant effects 
on cardiovascular, gastrointestinal and CNS functions. The peptide was first 
isolated from the porcine spinal cord and later shown to be present in spinal 
cords of other species. Little is known about the distribution of neuromedin U 
receptors (NMURs) in the spinal cord and the spinal action of the peptide. Here 
we report on the expression of NMURs and a potential role in nociception in the 
rat spinal cord using a combination of behavioral and electrophysiological 
studies. Receptor autoradiography showed that NMU-23 binding was restricted to 
the superficial layers of spinal cord, a region known to be involved in the 
control of nociception. In situ hybridization analysis indicated the mRNA of 
NMUR2 was located in the same region (laminae I and IIo) as NMU-23 binding, 
while the mRNA for NMU receptor 1 was observed in a subpopulation of small 
diameter neurons of dorsal root ganglia. Intrathecal (i.t.) administration of 
neuromedin U-23 (0.4-4.0 nmol/10 microl) dose-dependently decreased both the 
mechanical threshold to von Frey hair stimulation and the withdrawal latency to 
a noxious thermal stimulus. Mechanical allodynia was observed between 10 and 120 
min, peaking at 30 min and heat hyperalgesia was observed 10-30 min after i.t. 
administration of NMU-23. A similar mechanical allodynia was also observed 
following i.t. administration of NMU-8 (0.4-4 nmol/10 microl). A significant 
enhancement of the excitability of flexor reflex was induced by intrathecal 
administration of NMU-23 (4 nmol/10 microl). Evoked responses to touch and pinch 
stimuli were increased by 439+/-94% and 188+/-36% (P<0.01, n=6) respectively. 
The behavioral and electrophysiological data demonstrate, for the first time, a 
pro-nociceptive action of NMU. The restricted distribution of NMU receptors to a 
region of the spinal cord involved in nociception suggests that this peptide 
receptor system may play a role in nociception.