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      Elevated Production of Nociceptive CC Chemokines and sE-Selectin in Patients With Low Back Pain and the Effects of Spinal Manipulation : A Nonrandomized Clinical Trial

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          Abstract

          Background:

          The involvement of inflammatory components in the pathophysiology of low back pain (LBP) is poorly understood. It has been suggested that spinal manipulative therapy (SMT) may exert anti-inflammatory effects.

          Purpose:

          The purpose of this study was to determine the involvement of inflammation-associated chemokines (CC series) in the pathogenesis of nonspecific LBP and to evaluate the effect of SMT on that process.

          Methods:

          Patients presenting with nonradicular, nonspecific LBP (minimum pain score 3 on 10-point visual analog scale) were recruited according to stringent inclusion criteria. They were evaluated for appropriateness to treat using a high velocity low amplitude manipulative thrust in the lumbar-lumbosacral region. Blood samples were obtained at baseline and following the administration of a series of 6 high velocity low amplitude manipulative thrusts on alternate days over the period of 2 weeks. The in vitro levels of CC chemokine ligands (CCL2, CCL3, and CCL4) production and plasma levels of an inflammatory biomarker, soluble E-selectin (sE-selectin), were determined at baseline and at the termination of treatments 2 weeks later.

          Results:

          Compared with asymptomatic controls baseline production of all chemokines was significantly elevated in acute ( P=0.004 to <0.0001), and that of CCL2 and CCL4 in chronic LBP patients ( P<0.0001). Furthermore, CCL4 production was significantly higher ( P<0.0001) in the acute versus chronic LBP group. sE-selectin levels were significantly higher ( P=0.003) in chronic but not in acute LBP patients. Following SMT, patient-reported outcomes showed significant ( P<0.0001) improvements in visual analog scale and Oswestry Disability Index scores. This was accompanied by a significant decline in CCL3 production ( P<0.0001) in both groups of patients. Change scores for CCL4 production differed significantly ( P<0.0001) only for the acute LBP cohort, and no effect on the production of CCL2 or plasma sE-selectin levels was noted in either group.

          Conclusions:

          The production of chemotactic cytokines is significantly and protractedly elevated in LBP patients. Changes in chemokine production levels, which might be related to SMT, differ in the acute and chronic LBP patient cohorts.

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          Most cited references31

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          Statistical Power Analysis for the Behavioral Sciences

          <i>Statistical Power Analysis</i> is a nontechnical guide to power analysis in research planning that provides users of applied statistics with the tools they need for more effective analysis. The Second Edition includes: <br> * a chapter covering power analysis in set correlation and multivariate methods;<br> * a chapter considering effect size, psychometric reliability, and the efficacy of "qualifying" dependent variables and;<br> * expanded power and sample size tables for multiple regression/correlation.<br>
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            Role of cytokines in intervertebral disc degeneration: pain and disc content.

            Degeneration of the intervertebral discs (IVDs) is a major contributor to back, neck and radicular pain. IVD degeneration is characterized by increases in levels of the proinflammatory cytokines TNF, IL-1α, IL-1β, IL-6 and IL-17 secreted by the IVD cells; these cytokines promote extracellular matrix degradation, chemokine production and changes in IVD cell phenotype. The resulting imbalance in catabolic and anabolic responses leads to the degeneration of IVD tissues, as well as disc herniation and radicular pain. The release of chemokines from degenerating discs promotes the infiltration and activation of immune cells, further amplifying the inflammatory cascade. Leukocyte migration into the IVD is accompanied by the appearance of microvasculature tissue and nerve fibres. Furthermore, neurogenic factors, generated by both disc and immune cells, induce expression of pain-associated cation channels in the dorsal root ganglion. Depolarization of these ion channels is likely to promote discogenic and radicular pain, and reinforce the cytokine-mediated degenerative cascade. Taken together, an enhanced understanding of the contribution of cytokines and immune cells to these catabolic, angiogenic and nociceptive processes could provide new targets for the treatment of symptomatic disc disease. In this Review, the role of key inflammatory cytokines during each of the individual phases of degenerative disc disease, as well as the outcomes of major clinical studies aimed at blocking cytokine function, are discussed.
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              The mechanisms of manual therapy in the treatment of musculoskeletal pain: a comprehensive model.

              Prior studies suggest manual therapy (MT) as effective in the treatment of musculoskeletal pain; however, the mechanisms through which MT exerts its effects are not established. In this paper we present a comprehensive model to direct future studies in MT. This model provides visualization of potential individual mechanisms of MT that the current literature suggests as pertinent and provides a framework for the consideration of the potential interaction between these individual mechanisms. Specifically, this model suggests that a mechanical force from MT initiates a cascade of neurophysiological responses from the peripheral and central nervous system which are then responsible for the clinical outcomes. This model provides clear direction so that future studies may provide appropriate methodology to account for multiple potential pertinent mechanisms.
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                Author and article information

                Journal
                Clin J Pain
                Clin J Pain
                AJP
                The Clinical Journal of Pain
                Lippincott Williams & Wilkins
                0749-8047
                1536-5409
                January 2018
                06 December 2017
                : 34
                : 1
                : 68-75
                Affiliations
                [* ]Graduate Education and Research Programs
                []Department of Pathology and Microbiology, Canadian Memorial Chiropractic College, Toronto, ON, Canada
                Author notes
                Reprints: Stephen H. Injeyan, PhD, DC, Canadian Memorial Chiropractic College, 6100 Leslie Street, Toronto, ON, Canada M2H 3J1 (e-mail: sinjeyan@ 123456cmcc.ca ).
                Article
                10.1097/AJP.0000000000000507
                5728592
                29200015
                d8bcb7e4-c1da-4f7a-a8b0-3609f7b35447
                Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/

                History
                : 4 November 2016
                : 6 March 2017
                : 15 April 2017
                Categories
                Original Articles
                Custom metadata
                TRUE

                low back pain,cc chemokines,se-selectin,spinal manipulation,inflammation

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