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Mice genetically deficient in neuromedin U receptor 2, but not neuromedin U receptor 1, have impaired nociceptive responses

Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA.
Pain (Impact Factor: 5.84). 09/2007; 130(3):267-78. DOI: 10.1016/j.pain.2007.01.036
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ABSTRACT 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.

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Available from: Mark Sleeman, Aug 18, 2015
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    • "Surprisingly, both Nmur1 À/À and Nmu À/À mice demonstrated a normal response to intraplantar CFA administration, although some modest differences in serum cytokine induction were noted. Torres et al. also recently reported normal paw swelling and nociception in a CFA-induced pain model using Nmur1 À/À mice [8]. Together, these studies demonstrate that Nmur1 À/À mice are not protected from CFA-induced cutaneous inflammation and do not support a major role for Nmur1 in mediating the reported inflammatory functions of NmU. "
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