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      Pain modulation in the spinal cord

      review-article
      * ,
      Frontiers in Pain Research
      Frontiers Media S.A.
      pain, spinal cord, gate control theory, inhibition, presynaptic

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          Abstract

          The sensory inflow from the periphery that triggers innocuous and painful sensations is highly complex, capturing key elements of the nature of any stimulus, its location, intensity, and duration, and converting this to dynamic action potential firing across a wide population of afferents. While sensory afferents are highly specialized to detect these features, their input to the spinal cord also triggers active processing and modulation there which determines its output, to drive the sensory percept experienced and behavioral responses. Focus on such active spinal modulation was arguably first introduced by Melzack and Wall in their Spinal Cord Gate Control theory. This theory has had a profound influence on our understanding of pain, and especially its processing, as well as leading directly to the development of clinical interventions, and its historical importance certainly needs to be fully recognized. However, the enormous progress we are making in the understanding of the function of the somatosensory system, means that it is time to incorporate these newly discovered features into a more complex and accurate model of spinal sensory modulation.

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          Most cited references38

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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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            Transcriptional Reprogramming of Distinct Peripheral Sensory Neuron Subtypes after Axonal Injury

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              Deschloroclozapine, a potent and selective chemogenetic actuator enables rapid neuronal and behavioral modulations in mice and monkeys

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                Author and article information

                Contributors
                Journal
                Front Pain Res (Lausanne)
                Front Pain Res (Lausanne)
                Front. Pain Res.
                Frontiers in Pain Research
                Frontiers Media S.A.
                2673-561X
                2673-561X
                13 September 2022
                2022
                : 3
                : 984042
                Affiliations
                FM Kirby Neurobiology Center, Boston Children's Hospital and Department of Neurobiology, Harvard Medical School , Boston, MA, United States
                Author notes

                Edited by: Tony L. Yaksh, University of California, San Diego, United States

                Reviewed by: Judy Golden, Washington University in St. Louis, United States

                *Correspondence: Clifford J. Woolf clifford.woolf@ 123456childrens.harvard.edu

                This article was submitted to Pain Mechanisms, a section of the journal Frontiers in Pain Research

                Article
                10.3389/fpain.2022.984042
                9513129
                36176710
                cecc380d-eb41-4358-8ddc-ef3652518f14
                Copyright © 2022 Woolf.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 01 July 2022
                : 05 August 2022
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 38, Pages: 04, Words: 3543
                Categories
                Pain Research
                Mini Review

                pain,spinal cord,gate control theory,inhibition,presynaptic
                pain, spinal cord, gate control theory, inhibition, presynaptic

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