Mice genetically deficient in neuromedin U receptor 2, but not neuromedin U receptor 1, have impaired nociceptive responses.
Neuromedin U (NMU) has recently been reported to have a role in nociception and inflammation. To clarify the function of the two known NMU receptors, NMU receptor 1 (NMUR1) and NMU receptor 2 (NMUR2), during nociception and inflammation in vivo, we generated mice in which the genes for each receptor were independently deleted. Compared to wild type littermates, mice deficient in NMUR2 showed a reduced thermal nociceptive response in the hot plate, but not in the tail flick, test. In addition, the NMUR2 mutant mice showed a reduced behavioral response and a marked reduction in thermal hyperalgesia following capsaicin injection. NMUR2-deficient mice also showed an impaired pain response during the chronic, but not acute, phase of the formalin test. In contrast, NMUR1-deficient mice did not show any nociceptive differences compared to their wild type littermates in any of the behavioral tests used. We observed the same magnitude of inflammation in both lines of NMU receptor mutant mice compared to their wild type littermates after injection with complete Freund's adjuvant (CFA), suggesting no requirement for either receptor in this response. Thus, the pro-nociceptive effects of NMU in mice appear to be mediated through NMUR2, not NMUR1.
Torres
Richard
R
Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA Department of Psychology, Queens College of CUNY, 65-30 Kissena Blvd. Flushing, NY 11367, USA Neuropsychology & Neuroscience Subprograms, Graduate Center of CUNY, NY, USA.
Croll
Susan D
SD
Vercollone
Jeffrey
J
Reinhardt
Joel
J
Griffiths
Jennifer
J
Zabski
Stephanie
S
Anderson
Keith D
KD
Adams
Niels C
NC
Gowen
Lori
L
Sleeman
Mark W
MW
Valenzuela
David M
DM
Wiegand
Stanley J
SJ
Yancopoulos
George D
GD
Murphy
Andrew J
AJ
D000818:Animals; D001522:Behavior, Animal; D002211:Capsaicin; D005260:Female; D005620:Freund's Adjuvant; D015870:Gene Expression; D006358:Hot Temperature; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009619:Nociceptors / Q000502:physiology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000235:genetics* / Q000502:physiology*
D008565:Membrane Proteins; D017981:Receptors, Neurotransmitter; C082444:neuromedin U receptor; D005620:Freund's Adjuvant; D002211:Capsaicin