{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T17:21:57Z","timestamp":1787851317638,"version":"build-2784847793"},"reference-count":15,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T00:00:00Z","timestamp":1695254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Marian University College of Osteopathic Medicine Faculty Research Development award"},{"name":"other intramural funds"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Low back pain (LBP) is a common musculoskeletal complaint that can impede physical function and mobility. Current management often involves pain medication, but there is a need for non-pharmacological and non-invasive interventions. Soft tissue manipulation (STM), such as massage, has been shown to be effective in human subjects, but the molecular mechanisms underlying these findings are not well understood. In this paper, we evaluated potential changes in the soft tissue levels of more than thirty pro- or anti-inflammatory cytokines following instrument-assisted STM (IASTM) in rats with chronic, induced LBP using Complete Freund\u2019s Adjuvant. Our results indicate that IASTM is associated with reduced soft tissue levels of Regulated on Activation, Normal T cell Expressed and Secreted (RANTES)\/Chemokine (C-C motif) ligand 5 (CCL5) and increased soft tissue levels of Interleukin (IL)-4, which are pro-inflammatory and anti-inflammatory factors, respectively, by 120 min post-treatment. IASTM was not associated with tissue-level changes in C-X-C Motif Chemokine Ligand (CXCL)-5\/Lipopolysaccharide-Induced CXC Chemokine (LIX)\u2013which is the murine homologue of IL-8, CXCL-7, Granulocyte-Macrophage-Colony Simulating Factor (GM-CSF), Intercellular Adhesion Molecule (ICAM)-1, IL1-Receptor Antagonist (IL-1ra), IL-6, Interferon-Inducible Protein (IP)-10\/CXCL-10, L-selectin, Tumor Necrosis Factor (TNF)-\u03b1, or Vascular Endothelial Growth Factor (VEGF) at either 30 or 120 min post-treatment. Combined, our findings raise the possibility that IASTM may exert tissue-level effects associated with improved clinical outcomes and potentially beneficial changes in pro-\/anti-inflammatory cytokines in circulation and at the tissue level.<\/jats:p>","DOI":"10.3390\/ijms241814392","type":"journal-article","created":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T21:08:36Z","timestamp":1695330516000},"page":"14392","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Soft Tissue Manipulation Alters RANTES\/CCL5 and IL-4 Cytokine Levels in a Rat Model of Chronic Low Back Pain"],"prefix":"10.3390","volume":"24","author":[{"given":"Carmela L.","family":"Marciano","sequence":"first","affiliation":[{"name":"Division of Biomedical Science, College of Osteopathic Medicine, Marian University, Indianapolis, IN 46222, USA"},{"name":"Bone & Muscle Research Group, Marian University, Indianapolis, IN 46222, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor A.","family":"Hiland","sequence":"additional","affiliation":[{"name":"Division of Biomedical Science, College of Osteopathic Medicine, Marian University, Indianapolis, IN 46222, USA"},{"name":"Bone & Muscle Research Group, Marian University, Indianapolis, IN 46222, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krista L.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Division of Biomedical Science, College of Osteopathic Medicine, Marian University, Indianapolis, IN 46222, USA"},{"name":"Bone & Muscle Research Group, Marian University, Indianapolis, IN 46222, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sierra","family":"Street","sequence":"additional","affiliation":[{"name":"Division of Biomedical Science, College of Osteopathic Medicine, Marian University, Indianapolis, IN 46222, USA"},{"name":"Bone & Muscle Research Group, Marian University, Indianapolis, IN 46222, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carson","family":"Maris","sequence":"additional","affiliation":[{"name":"Bone & Muscle Research Group, Marian University, Indianapolis, IN 46222, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Ehrsam","sequence":"additional","affiliation":[{"name":"Division of Biomedical Science, College of Osteopathic Medicine, Marian University, Indianapolis, IN 46222, USA"},{"name":"Bone & Muscle Research Group, Marian University, Indianapolis, IN 46222, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4703-7428","authenticated-orcid":false,"given":"Julia M.","family":"Hum","sequence":"additional","affiliation":[{"name":"Division of Biomedical Science, College of Osteopathic Medicine, Marian University, Indianapolis, IN 46222, USA"},{"name":"Bone & Muscle Research Group, Marian University, Indianapolis, IN 46222, USA"},{"name":"Indiana Biosciences Research Institute, Indianapolis, IN 46222, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2286-0733","authenticated-orcid":false,"given":"Mary Terry","family":"Loghmani","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, School of Health and Human Sciences, Indiana University, Indianapolis, IN 46222, USA"},{"name":"Indiana Center for Musculoskeletal Health, School of Medicine, Indiana University, Indianapolis, IN 46222, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tien-Min G.","family":"Chu","sequence":"additional","affiliation":[{"name":"Indiana Center for Musculoskeletal Health, School of Medicine, Indiana University, Indianapolis, IN 46222, USA"},{"name":"Department of Biomedical Sciences and Comprehensive Care, School of Dentistry, Indiana University, Indianapolis, IN 46222, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung S.","family":"Kang","sequence":"additional","affiliation":[{"name":"Bone & Muscle Research Group, Marian University, Indianapolis, IN 46222, USA"},{"name":"Indiana Biosciences Research Institute, Indianapolis, IN 46222, USA"},{"name":"Witchger School of Engineering, Marian University, Indianapolis, IN 46222, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9942-2945","authenticated-orcid":false,"given":"Jonathan W.","family":"Lowery","sequence":"additional","affiliation":[{"name":"Division of Biomedical Science, College of Osteopathic Medicine, Marian University, Indianapolis, IN 46222, USA"},{"name":"Bone & Muscle Research Group, Marian University, Indianapolis, IN 46222, USA"},{"name":"Indiana Biosciences Research Institute, Indianapolis, IN 46222, USA"},{"name":"Indiana Center for Musculoskeletal Health, School of Medicine, Indiana University, Indianapolis, IN 46222, USA"},{"name":"Division of Academic Affairs, Marian University, Indianapolis, IN 46222, USA"},{"name":"Department of Orthopaedic Surgery, School of Medicine, Indiana University, Indianapolis, IN 46222, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,21]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Back, Lower Limb, and Upper Limb Pain Among U.S. Adults, 2019","volume":"415","author":"Lucas","year":"2021","journal-title":"NCHS Data Brief"},{"key":"ref_2","first-page":"1067","article-title":"Chronic low back pain: Evaluation and management","volume":"79","author":"Last","year":"2009","journal-title":"Am. 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