{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:54:21Z","timestamp":1790636061250,"version":"4.1.0"},"reference-count":132,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2018,9,9]],"date-time":"2018-09-09T00:00:00Z","timestamp":1536451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundaci\u00f3n Universidad Cat\u00f3lica de Valencia San Vicente M\u00e1rtir","award":["2018-121-001"],"award-info":[{"award-number":["2018-121-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Application of protocols without parameter standardization and appropriate controls has led manual therapy (MT) and other physiotherapy-based approaches to controversial outcomes. Thus, there is an urgency to carefully define standard protocols that elevate physiotherapy treatments to rigorous scientific demands. One way in which this can be achieved is by studying gene expression and physiological changes that associate to particular, parameter-controlled, treatments in animal models, and translating this knowledge to properly designed, objective, quantitatively-monitored clinical trials (CTs). Here, we propose a molecular physiotherapy approach (MPTA) requiring multidisciplinary teams, to uncover the scientific reasons behind the numerous reports that historically attribute health benefits to MT-treatments. The review focuses on the identification of MT-induced physiological and molecular responses that could be used for the treatment of fibromyalgia (FM) and chronic fatigue syndrome\/myalgic encephalomyelitis (CFS\/ME). The systemic effects associated to mechanical-load responses are considered of particular relevance, as they suggest that defined, low-pain anatomic areas can be selected for MT treatment and yet yield overall benefits, an aspect that might result in it being essential to treat FM. Additionally, MT can provide muscle conditioning to sedentary patients without demanding strenuous physical effort, which is particularly detrimental for CFS\/ME patients, placing MT as a real option for integrative medicine programs to improve FM and CFS\/ME.<\/jats:p>","DOI":"10.3390\/ijms19092673","type":"journal-article","created":{"date-parts":[[2018,9,10]],"date-time":"2018-09-10T10:28:57Z","timestamp":1536575337000},"page":"2673","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Unraveling the Molecular Determinants of Manual Therapy: An Approach to Integrative Therapeutics for the Treatment of Fibromyalgia and Chronic Fatigue Syndrome\/Myalgic Encephalomyelitis"],"prefix":"10.3390","volume":"19","author":[{"given":"Jos\u00e9 Andr\u00e9s","family":"Espejo","sequence":"first","affiliation":[{"name":"School of Experimental Sciences, Universidad Cat\u00f3lica de Valencia San Vicente M\u00e1rtir, 46001 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5522-056X","authenticated-orcid":false,"given":"Mar\u00eda","family":"Garc\u00eda-Escudero","sequence":"additional","affiliation":[{"name":"School of Physiotherapy, Universidad Cat\u00f3lica de Valencia San Vicente M\u00e1rtir, 46900 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0598-2907","authenticated-orcid":false,"given":"Elisa","family":"Oltra","sequence":"additional","affiliation":[{"name":"School of Medicine, Universidad Cat\u00f3lica de Valencia San Vicente M\u00e1rtir, 46001 Valencia, Spain"},{"name":"Unidad Mixta CIPF-UCV, Centro de Investigaci\u00f3n Pr\u00edncipe Felipe, 46012 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2476","DOI":"10.1016\/S0140-6736(16)31851-7","article-title":"Revising the ICD: Explaining the WHO approach","volume":"388","author":"Boerma","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/art.1780330203","article-title":"The American College of Rheumatology 1990 Criteria for the Classification of fibromyalgia. 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