{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T06:08:58Z","timestamp":1775628538577,"version":"3.50.1"},"reference-count":76,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Rehabil. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Spinal manipulation (SM) may modulate immune and inflammatory responses in healthy and\/or musculoskeletal pain populations, yet SM responses in neurodegenerative populations such as multiple sclerosis are essentially unknown. This pilot study estimated the potential effects of chiropractic thoracic SM combined with trigger point therapy on serum inflammatory cytokine\/chemokine levels, neurodegeneration biomarkers, and clinical\/performance-based outcomes in people with relapsing-remitting multiple sclerosis (RRMS). The goal was to inform the design of future research.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This pilot randomized, sham-controlled trial included 21 RRMS participants assigned to either SM (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200911) or sham-SM (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910) groups. Interventions were delivered twice weekly for four weeks. Blood samples were collected at five timepoints: baseline (T0), 20\u2005min and 2\u2005h after first intervention (T1 and T2 respectively), and 20\u2005min and 2\u2005h after the final intervention (T3 and T4 respectively). Overall 21 inflammatory biomarkers, 3 neurodegenerative biomarkers and 12 clinical\/performance outcomes were assessed. Between-group differences were evaluated by comparing change scores from baseline per group, and effect sizes were reported using Cohen's\n                      <jats:italic>d<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eight cytokines\/chemokines in the SM group demonstrated moderate to large effect sizes (d\u2009\u2265\u20090.5) at a single timepoint post-intervention compared with the sham-SM group, whereas six (IL-8, IL-17A, GM-CSF, MIP-1\u03b2, IFN\n                      <jats:italic>\u03b3<\/jats:italic>\n                      , Fractalkine) demonstrated moderate to large effect sizes at multiple timepoints post-intervention. Among neurodegeneration biomarkers, t-tau levels decreased in the SM group with a small effect size (d\u2009=\u2009\u22120.42). Most clinical- and performance-based outcomes had small effect sizes with the few moderate effect size changes being below clinical relevance thresholds.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identified six cytokines\/chemokines that had moderate to large effect sizes at multiple post-intervention timepoints favoring SM. Of these biomarkers, all are considered to be primarily pro-inflammatory. Such results support appropriately powered randomized controlled trials of SM in RRMS population that focus on evaluating these cytokines\/chemokines across multiple timepoints including immediately (&amp;lt; 5\u2005min), intermediately (&amp;lt; 30\u2005min), and short-duration (\u22652\u2005h) post-intervention and seek to determine the contribution of soft tissue stimulation (i.e., trigger point therapy) preceding the SM to cytokine\/chemokine response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/clinicaltrials.gov\/<\/jats:ext-link>\n                      NCT04972929, registration date: April 27, 2021.\n                    <\/jats:p>\n                  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