{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:50:44Z","timestamp":1790376644512,"version":"4.1.0"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T00:00:00Z","timestamp":1610064000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T00:00:00Z","timestamp":1610064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canadian Memorial Chiropractic College"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Chiropr Man Therap"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The inflammatory profiles of patients with acute and chronic nonspecific low back pain (LBP) patients are distinct. Spinal manipulative therapy (SMT) has been shown to modulate the production of nociceptive chemokines differently in these patient cohorts. The present study further investigates the effect(s) of SMT on other inflammatory mediators in the same LBP patient cohorts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Acute (<jats:italic>n<\/jats:italic>\u00a0=\u200922) and chronic (<jats:italic>n<\/jats:italic>\u00a0=\u200925) LBP patients with minimum pain scores of 3 on a 10-point numeric scale, and asymptomatic controls (<jats:italic>n<\/jats:italic>\u00a0=\u200924) were recruited according to stringent exclusion criteria. Blood samples were obtained at baseline and after 2\u2009weeks during which patients received 6 SMTs in the lumbar or lumbosacral region. The in vitro production of tumor necrosis factor (TNF\u03b1), interleukin-1 \u03b2 (IL-1\u03b2), IL-6, IL-2, interferon \u0263 (IFN\u0263), IL-1 receptor antagonist (IL-1RA), TNF soluble receptor type 2 (sTNFR2) and IL-10 was determined by specific immunoassays. Parametric as well as non-parametric statistics (PAST 3.18 beta software) was used to determine significance of differences between and within study groups prior and post-SMT. Effect size (ES) estimates were obtained using Cohen\u2019s<jats:italic>d.<\/jats:italic><\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with asymptomatic controls, SMT-related change scores were significant (<jats:italic>P<\/jats:italic>\u00a0=\u20090.03\u20130.01) in reducing the production levels of TNF\u03b1 in both patient cohorts and those of IL-6, IFN\u0263 and sTNFR2 (<jats:italic>P<\/jats:italic>\u00a0=\u20090.001\u20130.02) in patients with chronic LBP. Above-moderate to large ES (<jats:italic>d<\/jats:italic>\u00a0&gt;\u20090.6\u20131.4) was observed for these mediators. Compared with respective baselines, a significant post-SMT reduction (<jats:italic>P<\/jats:italic>\u00a0=\u20090.01) of IL-6 production was detected only in patients with chronic LBP while a significant increase of IL-2 production (<jats:italic>P<\/jats:italic>\u00a0=\u20090.001 vs. control, and<jats:italic>P<\/jats:italic>\u00a0=\u20090.004 vs. chronic LBP group) and a large ES (<jats:italic>d\u2009=<\/jats:italic>\u00a00.87) were observed in patients with acute LBP. Pain and disability scores declined significantly (<jats:italic>P<\/jats:italic>\u00a0&lt;\u20090.001) in all LBP patients, and were positively correlated (<jats:italic>P<\/jats:italic>\u00a0=\u20090.03) with IFN\u0263 and IL-2 levels in the acute LBP cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The short course of SMT treatments of non-specific LBP patients resulted in significant albeit limited and diverse alterations in the production of several of the mediators investigated in this study. This exploratory study highlights the potential of SMT to modulate the production of inflammatory components in acute and chronic non-specific LBP patients and suggests a need for further, randomized controlled clinical trials in this area.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration<\/jats:title><jats:p>This study was prospectively registered April 2012 with Clinical Trials.gov (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01766141\">#NCT01766141<\/jats:ext-link>).<\/jats:p><jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/register.clinicaltrials.gov\/prs\/app\/action\/SelectProtocol?sid=S0003ZIL&amp;selectaction=Edit&amp;uid=U0001V74&amp;ts=2&amp;cx=-axvqtg\">https:\/\/register.clinicaltrials.gov\/prs\/app\/action\/SelectProtocol?sid=S0003ZIL&amp;selectaction=Edit&amp;uid=U0001V74&amp;ts=2&amp;cx=-axvqtg<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1186\/s12998-020-00357-y","type":"journal-article","created":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T00:16:29Z","timestamp":1610064989000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Effects of spinal manipulative therapy on inflammatory mediators in patients with non-specific low back pain: a non-randomized controlled clinical trial"],"prefix":"10.1186","volume":"29","author":[{"given":"Julita A.","family":"Teodorczyk-Injeyan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"Triano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Gringmuth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"DeGraauw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Chow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3694-2003","authenticated-orcid":false,"given":"H. Stephen","family":"Injeyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,8]]},"reference":[{"key":"357_CR1","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1016\/j.spinee.2018.01.013","volume":"18","author":"ID Coulter","year":"2018","unstructured":"Coulter ID, Crawford C, Hurwitz E, Vernon H, Khorsan R, Booth MS, Herman PM. Manipulation and mobilization for treating chronic low back pain: a systematic review and meta-analysis. The Spine J. 2018;18:866\u201379.","journal-title":"The Spine J"},{"key":"357_CR2","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1001\/jama.2017.3086","volume":"317","author":"NM Paige","year":"2017","unstructured":"Paige NM, Miake-Lie IM, Booth MS, Beroes JM, Mardian AS, Dougherty P, et al. Association of spinal manipulative therapy with clinical benefit and harm for acute low back pain. Systematic review and meta-analysis. JAMA. 2017;317:1451\u201361.","journal-title":"JAMA"},{"key":"357_CR3","doi-asserted-by":"publisher","first-page":"514","DOI":"10.7326\/M16-2367","volume":"166","author":"A Quaseem","year":"2017","unstructured":"Quaseem A, Wilt TJ, McLean RM, Forciea MA. Non-invasive treatments for acute, subacute, and chronic low back pain: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2017;166:514\u201330.","journal-title":"Ann Intern Med"},{"key":"357_CR4","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1067\/mmt.2002.123166","volume":"25","author":"DW Evans","year":"2002","unstructured":"Evans DW. Mechanisms and effects of spinal high-velocity low-amplitude thrust manipulation: previous theories. J Manip Physiol Ther. 2002;25:251\u201362.","journal-title":"J Manip Physiol Ther"},{"key":"357_CR5","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.jmpt.2016.02.011","volume":"39","author":"SJ Currie","year":"2016","unstructured":"Currie SJ, Myers CA, Durso C, Enebo BA, Davidson BS. The neuromuscular response to spinal manipulation in the presence of pain. J Manip Physiol Ther. 2016;39:288\u201393.","journal-title":"J Manip Physiol Ther"},{"key":"357_CR6","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/j.math.2008.09.001","volume":"14","author":"JE Bialosky","year":"2009","unstructured":"Bialosky JE, Bishop MD, Price DD, Robinson ME, George SZ. The mechanisms of manual therapy in the treatment of musculoskeletal pain: a comprehensive model. Man Ther. 2009;14:531\u20138.","journal-title":"Man Ther"},{"key":"357_CR7","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.jbmt.2010.03.004","volume":"14","author":"W Herzog","year":"2010","unstructured":"Herzog W. The biomechanics of spinal manipulation. J Body Mov Ther. 2010;14:280\u20136.","journal-title":"J Body Mov Ther"},{"key":"357_CR8","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1016\/j.mehy.2015.10.003","volume":"85","author":"KK Sampath","year":"2015","unstructured":"Sampath KK, Mani R, Cotter JD, Tumilty S. Measurable changes in the neuro-endocrinal mechanisms following spinal manipulation. Med Hypotheses. 2015;85:819\u201324.","journal-title":"Med Hypotheses"},{"key":"357_CR9","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1016\/S0140-6736(16)30970-9","volume":"389","author":"C Maher","year":"2017","unstructured":"Maher C, Underwood M, Buchbinder R. Nonspecific low back pain. Lancet. 2017;389:736\u201347.","journal-title":"Lancet"},{"key":"357_CR10","doi-asserted-by":"publisher","first-page":"2356","DOI":"10.1016\/S0140-6736(18)30480-X","volume":"391","author":"J Hartvigsen","year":"2018","unstructured":"Hartvigsen J, Hancock MJ, Kongsted A, Louw Q, Ferreira M, Genevay S, et al. What low back pain is and why we need to pay attention. Lancet. 2018;391:2356\u201367.","journal-title":"Lancet"},{"key":"357_CR11","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1016\/j.ejpain.2005.11.005","volume":"10","author":"K Gebhardt","year":"2006","unstructured":"Gebhardt K, Brenner H, Sturmer T, Raum E, Richter W, Schiltenwolf M, Buchner M. The course of high-sensitive C-reactive protein in correlation with pain and clinical function in patients with acute lumbosciatic pain and chronic low back pain - a 6 months prospective longitudinal study. Eur J Pain. 2006;10:711\u20139.","journal-title":"Eur J Pain"},{"issue":"art","key":"357_CR12","doi-asserted-by":"publisher","first-page":"e00361","DOI":"10.1042\/BSR20160187","volume":"36","author":"Y Li","year":"2016","unstructured":"Li Y, Liu J, Liu ZZ, Duanet DP. Inflammation in low back pain may be detected from the peripheral blood: suggestions for biomarker. Biosci Rep. 2016;36(art):e00361.","journal-title":"Biosci Rep"},{"key":"357_CR13","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1007\/s00586-018-5490-7","volume":"27","author":"DM Klyne","year":"2018","unstructured":"Klyne DM, Barbe MF, van den Hoorn W, Hodges PW. ISSLS Prize in clinical science 2018: longitudinal analysis of inflammatory, psychological, and sleep-related factors following an acute low back pain episode - the good, the bad and the ugly. Eur Spine J. 2018;27:763\u201377.","journal-title":"Eur Spine J"},{"key":"357_CR14","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1097\/BRS.0000000000001214","volume":"41","author":"BZ de Queiroz","year":"2016","unstructured":"de Queiroz BZ, Pereira DS, Lopes RA, Carvalho FD, Silva JP, de Britto RNM, et al. Association between the plasma levels of mediators of inflammation with pain and disability in the elderly with acute low back pain: data from the back complaints in the elders. Spine. 2016;41:197\u2013203.","journal-title":"Spine"},{"key":"357_CR15","doi-asserted-by":"publisher","first-page":"2140","DOI":"10.1016\/j.spinee.2018.06.349","volume":"18","author":"R van der Berg","year":"2018","unstructured":"van der Berg R, Jongbloed EM, de Schepper EIT, Bierma-Zeinstra SMA, Koes BW, Luijsterburg PAJ. The association between pro-inflammatory biomarkers and non-specific low back pain. The Spine J. 2018;18:2140\u201351.","journal-title":"The Spine J"},{"key":"357_CR16","first-page":"399","volume":"14","author":"P Brennan","year":"1991","unstructured":"Brennan P, Kokjohn K, Kaltinger C, Lohr G, Glendening C, et al. Enhanced phagocytic respiratory burst induced by spinal manipulation: potential role for substance P. J Manip Physiol Ther. 1991;14:399\u2013408.","journal-title":"J Manip Physiol Ther"},{"key":"357_CR17","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.jmpt.2005.10.002","volume":"29","author":"JA Teodorczyk-Injeyan","year":"2006","unstructured":"Teodorczyk-Injeyan JA, Injeyan HS, Ruegg R. Spinal manipulative therapy reduces inflammatory cytokines but not substance P production in normal subjects. J Manip Physiol Ther. 2006;29:14\u201321.","journal-title":"J Manip Physiol Ther"},{"key":"357_CR18","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1097\/AJP.0000000000000507","volume":"34","author":"JA Teodorczyk-Injeyan","year":"2018","unstructured":"Teodorczyk-Injeyan JA, McGregor MM, Triano JJ, Injeyan HS. Elevated production of nociceptive CC-chemokines and s E-selectin in patients with low back pain and the effect of spinal manipulation: a non-randomized clinical trial. Clin J Pain. 2018;34:68\u201375.","journal-title":"Clin J Pain"},{"key":"357_CR19","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1097\/AJP.0000000000000745","volume":"35","author":"JA Teodorczyk-Injeyan","year":"2019","unstructured":"Teodorczyk-Injeyan JA, Triano JJ, Injeyan HS. Non-specific low back pain. Inflammatory profiles of patient with acute and chronic pain. Clin J Pain. 2019;35:818\u201325.","journal-title":"Clin J Pain"},{"key":"357_CR20","doi-asserted-by":"publisher","first-page":"2940","DOI":"10.1097\/00007632-200011150-00017","volume":"25","author":"JC Fairbank","year":"2000","unstructured":"Fairbank JC, Pynset PB. The Oswestry disability index. Spine. 2000;25:2940\u201352.","journal-title":"Spine"},{"key":"357_CR21","first-page":"4493","volume":"27","author":"C Leboeuf-Y de","year":"2004","unstructured":"Leboeuf-Y de C, Gronstvedt A, Borge JA, Lothe J, Magnesen E, Nilsson \u00d8, et al. The Nordic back pain subpopulation program: demographic and clinical predictors for outcome in patients receiving chiropractic treatment for persistent back pain. J Manip Physiol Ther. 2004;27:4493\u2013502.","journal-title":"J Manip Physiol Ther"},{"key":"357_CR22","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1016\/j.spinee.2013.07.468","volume":"14","author":"M Haas","year":"2014","unstructured":"Haas M, Vavrek D, Peterson D, Polissar N, Neradilek MB. Dose response and efficacy of spinal manipulation for care of chronic low back pain: a randomized controlled trial. The Spine J. 2014;14:1106\u201316.","journal-title":"The Spine J"},{"key":"357_CR23","volume-title":"Manual of diversified diagnostic and therapeutic procedures","author":"B Gleberzon","year":"2014","unstructured":"Gleberzon B, Ross K. Manual of diversified diagnostic and therapeutic procedures. Toronto: Canadian Memorial Chiropractic College; 2014."},{"key":"357_CR24","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/j.jmpt.2011.08.010","volume":"34","author":"JA Teodorczyk-Injeyan","year":"2011","unstructured":"Teodorczyk-Injeyan JA, Triano JJ, McGregor M, Woodhouse L, Injeyan HS. J elevated production of inflammatory mediators including nociceptive chemokines in neck pain patients: a cross sectional evaluation. Manipulative Physiol Ther. 2011;34:498\u2013505.","journal-title":"Manipulative Physiol Ther"},{"key":"357_CR25","volume-title":"Statistical power analysis for the behavioral sciences","author":"J Cohen","year":"1988","unstructured":"Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed. New Jersey: Lawrence Erlbaum Associates; 1988.","edition":"2"},{"key":"357_CR26","first-page":"1","volume":"4","author":"\u00d8 Hammer","year":"2001","unstructured":"Hammer \u00d8, Harper DA, Ryan PD. PAST: paleontological statistics software package for education and data analysis. Palaeontol Electron. 2001;4:1\u20139.","journal-title":"Palaeontol Electron"},{"key":"357_CR27","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.neuropharm.2014.10.027","volume":"96","author":"A Vezzani","year":"2015","unstructured":"Vezzani A, Viviani B. Neuromodulatory properties of inflammatory cytokines and their impact on neuronal excitability. Neuropharmacology. 2015;96:70\u201382.","journal-title":"Neuropharmacology"},{"key":"357_CR28","first-page":"878","volume":"2011","author":"J Scheller","year":"1813","unstructured":"Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. The pro- and anti-inflammatory properties of the cytokine interleukin 6. Biochim Biophys Acta. 1813;2011:878\u201388.","journal-title":"Biochim Biophys Acta"},{"key":"357_CR29","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1213\/01.ANE.0000055362.56604.78","volume":"96","author":"RF De Jongh","year":"2003","unstructured":"De Jongh RF, Vissers KC, Meert TF, Booij HDJ, De Deyne CS, Heylen RJ. The role of interleukin-6 in nociception and pain. Anesth Analg. 2003;96:1096\u2013103.","journal-title":"Anesth Analg"},{"key":"357_CR30","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s12931-014-0103-4","volume":"15","author":"AK Ravi","year":"2014","unstructured":"Ravi AK, Khurana S, Lemon J, Plumb J, Booth G, Healy L, et al. Increased levels of soluble inteleukin-6 receptor and CCL3 in COPD sputum. Resp Res. 2014;15:103.","journal-title":"Resp Res"},{"key":"357_CR31","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1182\/blood.V83.1.113.113","volume":"183","author":"H Tilg","year":"1994","unstructured":"Tilg H, Trehu E, Atkins MB, Dinarello CA, Mier JW. Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55. Blood. 1994;183:113\u20138.","journal-title":"Blood"},{"key":"357_CR32","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1111\/nyas.13551","volume":"1410","author":"AN Khan","year":"2017","unstructured":"Khan AN, Jacobsen HE, Khan J, Filippi CG, Levine M, Lehman RA, et al. Inflammatory biomarkers of low back pain and disc degeneration: a review. Ann N Y Acad Sci. 2017;1410:68\u201384.","journal-title":"Ann N Y Acad Sci"},{"key":"357_CR33","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1038\/sj.embor.7401099","volume":"8","author":"MF Bachmann","year":"2007","unstructured":"Bachmann MF, Oxenius A. Interleukin 2: from immunostimulation to immunoregulation and back again. EMBO Rep. 2007;8:1142\u20138.","journal-title":"EMBO Rep"},{"key":"357_CR34","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1189\/jlb.0612293","volume":"93","author":"I Shachar","year":"2013","unstructured":"Shachar I, Karin N. The dual roles of inflammatory cytokines and chemokines in the regulation of autoimmune diseases and their clinical implications. J Leukoc Biol. 2013;93:51\u201361.","journal-title":"J Leukoc Biol"},{"key":"357_CR35","doi-asserted-by":"publisher","first-page":"3707","DOI":"10.4049\/jimmunol.168.8.3707","volume":"168","author":"L Flaishon","year":"2002","unstructured":"Flaishon L, Topilski I, Shoseyov D, Omission C, Grabovsky V, Lapidot TG, et al. Cutting edge: anti-inflammatory properties of low levels of IFN\u0263. J Immunol. 2002;168:3707\u201311.","journal-title":"J Immunol"},{"key":"357_CR36","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.immuni.2008.11.014","volume":"30","author":"A Yu","year":"2009","unstructured":"Yu A, Zhu L, Altman NH, Malek TR. A low interleukin-2 receptor signaling threshold supports the development and homeostasis of T regulatory cells. Immunity. 2009;30:204\u201319.","journal-title":"Immunity"},{"key":"357_CR37","doi-asserted-by":"publisher","first-page":"1392","DOI":"10.1038\/sj.gt.3301992","volume":"10","author":"MZ Yao","year":"2003","unstructured":"Yao MZ, Gu JF, Wang JH, Sun LY, Liu H, Liu XY. Adenovirus-mediated interleukin-2 gene therapy of nociception. Gene Ther. 2003;10:1392\u20139.","journal-title":"Gene Ther"},{"key":"357_CR38","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/S1529-9430(02)00400-X","volume":"2","author":"JG Pickar","year":"2002","unstructured":"Pickar JG. Neurophysiological effects of spinal manipulation. The Spine. 2002;2:357\u201371.","journal-title":"The Spine"},{"key":"357_CR39","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/j.math.2010.03.012","volume":"15","author":"E Bicalho","year":"2010","unstructured":"Bicalho E, Setti JAP, Macagnan J, Cano JLR, Manffra EF. Immediate effects of a high-velocity spine manipulation in paraspinal muscles activity of nonspecific chronic low-back pain subjects. Manual Ther. 2010;15:469\u201375.","journal-title":"Manual Ther"},{"key":"357_CR40","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1016\/j.math.2014.02.007","volume":"19","author":"F Molina-Ortega","year":"2014","unstructured":"Molina-Ortega F, Lomas-Vega R, Hita-Contreras F, Manzano PG, Achalandabaso A, Ramos-Morcillo AJ, Mart\u00ednez-Amat A. Immediate effects of spinal manipulation on nitric oxide, substance P and pain perception. Manual Ther. 2014;19:411\u20137.","journal-title":"Manual Ther"},{"key":"357_CR41","doi-asserted-by":"crossref","first-page":"3498","DOI":"10.4049\/jimmunol.148.11.3498","volume":"148","author":"CF Calvo","year":"1992","unstructured":"Calvo CF, Chavanel G, Senik A. 1992. Substance P enhances IL-2 expression in activated human T cells. J Immunol. 1992;148:3498\u2013504.","journal-title":"J Immunol"},{"key":"357_CR42","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1016\/j.bbi.2007.03.008","volume":"21","author":"DM Nance","year":"2007","unstructured":"Nance DM, Sanders VM. Autonomic innervation and regulation of the immune system. Brain Behav Immun. 2007;21:736\u201345.","journal-title":"Brain Behav Immun"},{"key":"357_CR43","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1146\/annurev-immunol-020711-075015","volume":"30","author":"U Andersson","year":"2012","unstructured":"Andersson U, Tracey KJ. Reflex principles of immunological homeostasis. Ann Rev Immunol. 2012;30:313\u201335.","journal-title":"Ann Rev Immunol"},{"key":"357_CR44","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.1113\/jphysiol.2013.268573","volume":"592","author":"D Martelli","year":"2014","unstructured":"Martelli D, Yao ST, McKinley MJ, McAllen RM. Reflex control of inflammation by sympathetic nerves, not the vagus. J Physiol. 2014;592:1677\u201386.","journal-title":"J Physiol"},{"key":"357_CR45","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1002\/j.1532-2149.2012.00170.x","volume":"17","author":"CJ Itz","year":"2013","unstructured":"Itz CJ, Geurts JW, van Kleef M, Nelemans P. Clinical course of non-specific low back pain: a systematic review of prospective cohort studies set in primary care. Eur J Pain. 2013;17:5\u201315.","journal-title":"Eur J Pain"}],"container-title":["Chiropractic &amp; Manual Therapies"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12998-020-00357-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12998-020-00357-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12998-020-00357-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T05:49:51Z","timestamp":1697521791000},"score":1,"resource":{"primary":{"URL":"https:\/\/chiromt.biomedcentral.com\/articles\/10.1186\/s12998-020-00357-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,8]]},"references-count":45,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["357"],"URL":"https:\/\/doi.org\/10.1186\/s12998-020-00357-y","relation":{},"ISSN":["2045-709X"],"issn-type":[{"value":"2045-709X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,8]]},"assertion":[{"value":"26 June 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 November 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study was approved by the Research Ethics Board of the Canadian Memorial Chiropractic College (certificate # 1201X04). All participants signed Informed Consent.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"All authors declare that they have no conflict of interest to disclose regarding this manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3"}}