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      Journal of Pain Research (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on reporting of high-quality laboratory and clinical findings in all fields of pain research and the prevention and management of pain. Sign up for email alerts here.

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      Is Open Access

      Peripherally Induced Reconditioning of the Central Nervous System: A Proposed Mechanistic Theory for Sustained Relief of Chronic Pain with Percutaneous Peripheral Nerve Stimulation

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          Abstract

          Peripheral nerve stimulation (PNS) is an effective tool for the treatment of chronic pain, although its efficacy and utilization have previously been significantly limited by technology. In recent years, purpose-built percutaneous PNS devices have been developed to overcome the limitations of conventional permanently implanted neurostimulation devices. Recent clinical evidence suggests clinically significant and sustained reductions in pain can persist well beyond the PNS treatment period, outcomes that have not previously been observed with conventional permanently implanted neurostimulation devices. This narrative review summarizes mechanistic processes that contribute to chronic pain, and the potential mechanisms by which selective large diameter afferent fiber activation may reverse these changes to induce a prolonged reduction in pain. The interplay of these mechanisms, supported by data in chronic pain states that have been effectively treated with percutaneous PNS, will also be discussed in support of a new theory of pain management in neuromodulation: Peripherally Induced Reconditioning of the Central Nervous System (CNS).

          Most cited references187

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          Cellular and molecular mechanisms of pain.

          The nervous system detects and interprets a wide range of thermal and mechanical stimuli, as well as environmental and endogenous chemical irritants. When intense, these stimuli generate acute pain, and in the setting of persistent injury, both peripheral and central nervous system components of the pain transmission pathway exhibit tremendous plasticity, enhancing pain signals and producing hypersensitivity. When plasticity facilitates protective reflexes, it can be beneficial, but when the changes persist, a chronic pain condition may result. Genetic, electrophysiological, and pharmacological studies are elucidating the molecular mechanisms that underlie detection, coding, and modulation of noxious stimuli that generate pain.
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            Central sensitization: a generator of pain hypersensitivity by central neural plasticity.

            Central sensitization represents an enhancement in the function of neurons and circuits in nociceptive pathways caused by increases in membrane excitability and synaptic efficacy as well as to reduced inhibition and is a manifestation of the remarkable plasticity of the somatosensory nervous system in response to activity, inflammation, and neural injury. The net effect of central sensitization is to recruit previously subthreshold synaptic inputs to nociceptive neurons, generating an increased or augmented action potential output: a state of facilitation, potentiation, augmentation, or amplification. Central sensitization is responsible for many of the temporal, spatial, and threshold changes in pain sensibility in acute and chronic clinical pain settings and exemplifies the fundamental contribution of the central nervous system to the generation of pain hypersensitivity. Because central sensitization results from changes in the properties of neurons in the central nervous system, the pain is no longer coupled, as acute nociceptive pain is, to the presence, intensity, or duration of noxious peripheral stimuli. Instead, central sensitization produces pain hypersensitivity by changing the sensory response elicited by normal inputs, including those that usually evoke innocuous sensations. In this article, we review the major triggers that initiate and maintain central sensitization in healthy individuals in response to nociceptor input and in patients with inflammatory and neuropathic pain, emphasizing the fundamental contribution and multiple mechanisms of synaptic plasticity caused by changes in the density, nature, and properties of ionotropic and metabotropic glutamate receptors.
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              Pain Mechanisms: A New Theory

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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                jpr
                jpainres
                Journal of Pain Research
                Dove
                1178-7090
                12 March 2021
                2021
                : 14
                : 721-736
                Affiliations
                [1 ]The Spine and Nerve Center of the Virginias , Charleston, WV, USA
                [2 ]Department of Pain Medicine, The James Cook University Hospital , Middlesbrough, UK
                [3 ]Department of Neurosurgery, Neurosurgical Associates of Lancaster , Lancaster, PA, USA
                [4 ]Anesthesiology, Virginia Commonwealth University Medical Center , Richmond, VA, USA
                [5 ]Premier Pain Centers , Shrewsbury, NJ, USA
                [6 ]SPR Therapeutics , Cleveland, OH, USA
                Author notes
                Correspondence: Timothy R Deer The Spine and Nerve Center of the Virginias , 400 Court Street, Suite 100, Charleston, WV, 25301, USATel +1 304/347-6141Fax +1 304/347-6855 Email doctdeer@aol.com
                Author information
                http://orcid.org/0000-0001-8907-7730
                http://orcid.org/0000-0002-9250-1886
                http://orcid.org/0000-0003-3996-087X
                http://orcid.org/0000-0001-6181-0806
                http://orcid.org/0000-0002-7973-7990
                Article
                297091
                10.2147/JPR.S297091
                7966353
                33737830
                f1b9a1c0-694d-45ff-bdb8-5fe7a53ac97e
                © 2021 Deer et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 16 December 2020
                : 26 February 2021
                Page count
                Figures: 4, References: 187, Pages: 16
                Categories
                Review

                Anesthesiology & Pain management
                chronic pain,neuromodulation,peripheral nerve stimulation,cortical plasticity,peripherally induced reconditioning,mechanism of action

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