Molecular architecture of endocannabinoid signaling in the dorsal horn of the spinal cord mediating antinociception

Abstract

Event Abstract Back to Event Molecular architecture of endocannabinoid signaling in the dorsal horn of the spinal cord mediating antinociception Rita Nyilas1, Laura C. Gregg2, Ken Mackie3, Masahiko Watanabe4, Andreas Zimmer5, Andrea G. Hohmann2 and István Katona1* 1 Institute of Experimental Medicine, Hungarian Academy of Sciences, Hungary 2 Department of Psychology, University of Georgia, Georgia 3 Department of Psychological and Brain Sciences, Indiana University, United States 4 Department of Anatomy, Hokkaido University School of Medicine, Japan 5 Institute of Molecular Psychiatry, University of Bonn, Germany Cannabinoid receptor agonists exert a highly potent antinociceptive effect in acute and chronic pain indicating that endogenous cannabinoids may have a pivotal role in the regulation of nociception. However, the underlying molecular basis of endocannabinoid signaling has remained elusive at the spinal level. Because the lipid messenger 2-arachidonoylglycerol (2-AG) is emerging as a candidate molecule for being the predominant synaptic endocannabinoid, we aimed to characterize the precise molecular architecture of 2-AG signaling and its involvement in nociception in the spinal cord. Non-radioactive in situ hybridization revealed that dorsal horn neurons widely express the mRNA of diacylglycerol lipase-alpha (DGL-α), the synthesizing enzyme of 2-AG. Peroxidase-based immunocytochemistry demonstrated high levels of DGL-α protein and CB1 cannabinoid receptor, the receptor of 2-AG, in the superficial dorsal horn, at the first site of modulation of the ascending pain pathway. High-resolution immunoelectron microscopy uncovered presynaptic localization of CB1 and postsynaptic positioning of DGL-α at nociceptive synapses formed by Aδ- and C-fibers. Furthermore, DGL-α in postsynaptic elements receiving nociceptive inputs colocalized with metabotropic glutamate receptor 5 (mGluR5) known to trigger 2-AG release. Finally, intrathecal induction of mGluR5 evoked stress-induced analgesia through activation of DGL-α and CB1 in the spinal cord. Taken together, these findings underlie the key role of 2-AG-mediated retrograde suppression of nociceptive transmission at the spinal level. The striking positioning of the molecular players of 2-AG synthesis and action at nociceptive excitatory synapses suggests that pharmacological regulation of intrinsic spinal 2-AG levels may have important therapeutic potential in the regulation of pain sensation. Conference: 12th Meeting of the Hungarian Neuroscience Society, Budapest, Hungary, 22 Jan - 24 Jan, 2009. Presentation Type: Poster Presentation Topic: Pathophysiology and neurology - non-degenerative disorders Citation: Nyilas R, Gregg LC, Mackie K, Watanabe M, Zimmer A, Hohmann AG and Katona I (2009). Molecular architecture of endocannabinoid signaling in the dorsal horn of the spinal cord mediating antinociception. Front. Syst. Neurosci. Conference Abstract: 12th Meeting of the Hungarian Neuroscience Society. doi: 10.3389/conf.neuro.01.2009.04.035 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Feb 2009; Published Online: 27 Feb 2009. * Correspondence: István Katona, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary, katona@koki.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Rita Nyilas Laura C Gregg Ken Mackie Masahiko Watanabe Andreas Zimmer Andrea G Hohmann István Katona Google Rita Nyilas Laura C Gregg Ken Mackie Masahiko Watanabe Andreas Zimmer Andrea G Hohmann István Katona Google Scholar Rita Nyilas Laura C Gregg Ken Mackie Masahiko Watanabe Andreas Zimmer Andrea G Hohmann István Katona PubMed Rita Nyilas Laura C Gregg Ken Mackie Masahiko Watanabe Andreas Zimmer Andrea G Hohmann István Katona Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.