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While manual therapy (MT) is a clinically validated intervention, its capacity to modulate the neuro\u2010immune\u2010metabolic axis remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We established a complete Freund\u2019s adjuvant (CFA)\u2013induced CLBP rat model and used a combination of in vivo behavioral and molecular techniques to study MT intervention mechanisms. The therapeutic effects were evaluated via multidimensional approaches combining behavioral assays, histology, and high\u2010throughput dual\u2010tissue (prefrontal cortex and multifidus muscle) proteomics and metabolomics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MT intervention significantly attenuated mechanical hyperalgesia and suppressed pro\u2010inflammatory cytokines (IL\u20106, IL\u20101\u03b2, and TNF\u2010\u03b1) in muscle tissues. Integrated omics revealed distinct reprogramming of metabolic pathways, including GABAergic synapses and oxidative phosphorylation. Crucially, the CLBP model exhibited aberrant upregulation of autophagy initiation markers (AMPK, ULK1, and LC3B) coupled with substrate accumulation (p62), indicative of pathological autophagic stress. MT partially normalized the altered expression of autophagy\u2010related proteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings from a CFA\u2010induced inflammatory multifidus injury rat model suggest that AMPK\/ULK1\u2010linked autophagy signaling may correlate with the therapeutic effects of MT on inflammatory muscle\u2010type low back pain; these preclinical observations require further verification in heterogeneous clinical CLBP cohorts and multiple animal models.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/prm\/6688692","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T06:48:03Z","timestamp":1787813283000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Multiomics Analysis Reveals Manual Therapy Restores Autophagic 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