Y1 receptor knockout increases nociception and prevents the anti-allodynic actions of NPY.

Nutrition
K E KuphalBradley K Taylor

Abstract

Recent pharmacologic studies in our laboratory have suggested that the spinal neuropeptide Y (NPY) Y1 receptor contributes to pain inhibition and to the analgesic effects of NPY. To rule out off-target effects, the present study used Y1-receptor-deficient (-/-) mice to further explore the contribution of Y1 receptors to pain modulation. Y1(-/-) mice exhibited reduced latency in the hotplate test of acute pain and a longer-lasting heat allodynia in the complete Freund's adjuvant (CFA) model of inflammatory pain. Y1 deletion did not change CFA-induced inflammation. Upon targeting the spinal NPY systems with intrathecal drug delivery, NPY reduced tactile and heat allodynia in the CFA model and the partial sciatic nerve ligation model of neuropathic pain. Importantly, we show for the first time that NPY does not exert these anti-allodynic effects in Y1(-/-) mice. Furthermore, in nerve-injured CD1 mice, concomitant injection of the potent Y1 antagonist BIBO3304 prevented the anti-allodynic actions of NPY. Neither NPY nor BIBO3304 altered performance on the Rotorod test, arguing against an indirect effect of motor function. The Y1 receptor contributes to pain inhibition and to the analgesic effects of NPY.

References

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Citations

May 22, 2009·Current Pain and Headache Reports·Bradley K Taylor
Apr 13, 2011·Proceedings of the National Academy of Sciences of the United States of America·Brian SolwayBradley K Taylor
Sep 2, 2011·Neuropeptides·Laurie L Lemons, R G Wiley
Jun 23, 2011·Pharmacology, Biochemistry, and Behavior·Natalie L Trent, Janet L Menard
Nov 6, 2012·European Journal of Pharmacology·Suraj M YalamuriChristina M Spofford
Dec 30, 2006·Peptides·Peter A SmithBradley K Taylor
Feb 15, 2018·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Lauren C StrotherWeera Supronsinchai
Feb 10, 2017·Physiological Reviews·Peter J GoadsbySimon Akerman
Dec 29, 2020·Frontiers in Cellular Neuroscience·Emily L Tran, LaTasha K Crawford

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