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      Recent advances in our understanding of the organization of dorsal horn neuron populations and their contribution to cutaneous mechanical allodynia

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          Abstract

          The dorsal horns of the spinal cord and the trigeminal nuclei in the brainstem contain neuron populations that are critical to process sensory information. Neurons in these areas are highly heterogeneous in their morphology, molecular phenotype and intrinsic properties, making it difficult to identify functionally distinct cell populations, and to determine how these are engaged in pathophysiological conditions. There is a growing consensus concerning the classification of neuron populations, based on transcriptomic and transductomic analyses of the dorsal horn. These approaches have led to the discovery of several molecularly defined cell types that have been implicated in cutaneous mechanical allodynia, a highly prevalent and difficult-to-treat symptom of chronic pain, in which touch becomes painful. The main objective of this review is to provide a contemporary view of dorsal horn neuronal populations, and describe recent advances in our understanding of on how they participate in cutaneous mechanical allodynia.

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          The online version of this article (10.1007/s00702-020-02159-1) contains supplementary material, which is available to authorized users.

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          Transmitting pain and itch messages: a contemporary view of the spinal cord circuits that generate gate control.

          The original formulation of Gate Control Theory (GCT) proposed that the perception of pain produced by spinal cord signaling to the brain depends on a balance of activity generated in large (nonnociceptive)- and small (nociceptive)-diameter primary afferent fibers. The theory proposed that activation of the large-diameter afferent "closes" the gate by engaging a superficial dorsal horn interneuron that inhibits the firing of projection neurons. Activation of the nociceptors "opens" the gate through concomitant excitation of projection neurons and inhibition of the inhibitory interneurons. Sixty years after publication of the GCT, we are faced with an ever-growing list of morphologically and neurochemically distinct spinal cord interneurons. The present Review highlights the complexity of superficial dorsal horn circuitry and addresses the question whether the premises outlined in GCT still have relevance today. By examining the dorsal horn circuits that underlie the transmission of "pain" and "itch" messages, we also address the extent to which labeled lines can be incorporated into a contemporary view of GCT. Copyright © 2014 Elsevier Inc. All rights reserved.
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            Neural circuits for pain: Recent advances and current views

            The mammalian nervous system encodes many different forms of pain, from those that arise as a result of short-term low-grade interactions with noxious thermal, chemical, or mechanical sources to more serious forms of pain induced by trauma and disease. In this Review, we highlight recent advances in our understanding of the neural circuits that encode these types of pain. Promising therapeutic strategies based on recent advances are also highlighted.
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              A Brainstem-Spinal Cord Inhibitory Circuit for Mechanical Pain Modulation by GABA and Enkephalins.

              Pain thresholds are, in part, set as a function of emotional and internal states by descending modulation of nociceptive transmission in the spinal cord. Neurons of the rostral ventromedial medulla (RVM) are thought to critically contribute to this process; however, the neural circuits and synaptic mechanisms by which distinct populations of RVM neurons facilitate or diminish pain remain elusive. Here we used in vivo opto/chemogenetic manipulations and trans-synaptic tracing of genetically identified dorsal horn and RVM neurons to uncover an RVM-spinal cord-primary afferent circuit controlling pain thresholds. Unexpectedly, we found that RVM GABAergic neurons facilitate mechanical pain by inhibiting dorsal horn enkephalinergic/GABAergic interneurons. We further demonstrate that these interneurons gate sensory inputs and control pain through temporally coordinated enkephalin- and GABA-mediated presynaptic inhibition of somatosensory neurons. Our results uncover a descending disynaptic inhibitory circuit that facilitates mechanical pain, is engaged during stress, and could be targeted to establish higher pain thresholds. VIDEO ABSTRACT.
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                Author and article information

                Contributors
                cedric.peirs@inserm.fr
                Journal
                J Neural Transm (Vienna)
                J Neural Transm (Vienna)
                Journal of Neural Transmission
                Springer Vienna (Vienna )
                0300-9564
                1435-1463
                2 April 2020
                2 April 2020
                2020
                : 127
                : 4
                : 505-525
                Affiliations
                [1 ]GRID grid.411163.0, ISNI 0000 0004 0639 4151, Université Clermont Auvergne, CHU Clermont-Ferrand, Inserm, Neuro-Dol, ; Clermont-Ferrand, F-63000 France
                [2 ]GRID grid.8756.c, ISNI 0000 0001 2193 314X, Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, , University of Glasgow, ; Glasgow, G12 8QQ UK
                Author information
                http://orcid.org/0000-0002-2296-0323
                http://orcid.org/0000-0001-7494-116X
                http://orcid.org/0000-0002-3007-6749
                Article
                2159
                10.1007/s00702-020-02159-1
                7148279
                32239353
                6e93867d-0051-4e72-a989-c43bf57c3335
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 26 November 2019
                : 10 February 2020
                Funding
                Funded by: Institut National de la Santé et de la Recherche Médicale
                Categories
                Neurology and Preclinical Neurological Studies - Review Article
                Custom metadata
                © Springer-Verlag GmbH Austria, part of Springer Nature 2020

                dorsal horn,neurons,cutaneous mechanical allodynia,chronic pain

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