Genetic reduction of chronic muscle pain in mice lacking calcium/calmodulin-stimulated adenylyl cyclases

Molecular Pain
Kunjumon I VadakkanMin Zhuo

Abstract

The Ca2+/calmodulin-stimulated adenylyl cyclase (AC) isoforms AC1 and AC8, couple NMDA receptor activation to cAMP signaling pathways in neurons and are important for development, learning and memory, drug addiction and persistent pain. AC1 and AC8 in the anterior cingulate cortex (ACC) and the spinal cord were previously shown to be important in subcutaneous inflammatory pain. Muscle pain is different from cutaneous pain in its characteristics as well as conducting fibers. Therefore, we conducted the present work to test the role of AC1 and AC8 in both acute persistent and chronic muscle pain. Using an acute persistent inflammatory muscle pain model, we found that the behavioral nociceptive responses of both the late phase of acute muscle pain and the chronic muscle inflammatory pain were significantly reduced in AC1 knockout (KO) and AC1&8 double knockout (DKO) mice. Activation of other adenylyl cyclases in these KO mice by microinjection of forskolin into the ACC or spinal cord, but not into the peripheral tissue, rescued the behavioral nociceptive responses. Additionally, intra-peritoneal injection of an AC1 inhibitor significantly reduced behavioral responses in both acute persistent and chronic muscle pain. The results of...Continue Reading

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Citations

Sep 4, 2008·Current Pain and Headache Reports·Josimari M DeSantana, Kathleen A Sluka
Dec 25, 2012·The Journal of Biological Chemistry·Riad EfendievCarmen W Dessauer
Jan 14, 2011·Science Translational Medicine·Hansen WangMin Zhuo
Jul 18, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hui XuMin Zhuo
Jul 29, 2011·Medicine and Science in Sports and Exercise·Kathleen A SlukaLuis Felipe DaSilva
Apr 2, 2009·Nature Reviews. Drug Discovery·Sandra PierreKlaus Scholich
Sep 6, 2013·The Journal of Pharmacology and Experimental Therapeutics·Cameron S BrandCarmen W Dessauer
Sep 17, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Xu-Hui LiMin Zhuo
Oct 11, 2015·Molecular Brain·Zhen TianShui-Bing Liu
Sep 2, 2019·Neuroscience·Rafaela Silva Dos SantosGiovane Galdino
Mar 18, 2021·Translational Research : the Journal of Laboratory and Clinical Medicine·Joseph B O'Brien, David L Roman
Aug 9, 2021·Neuropharmacology·Qi-Yu ChenMin Zhuo

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