J Orthop Surg Res. 2025 Jul 8;20(1):622. doi: 10.1186/s13018-025-05986-8.ABSTRACTBACKGROUND: Fibromyalgia syndrome (FMS) is a chronic musculoskeletal disorder with unclear pathogenesis and a lack of targeted therapies. Central sensitization has emerged as a key mechanism that drives its pathophysiology. Although clinical studies support the efficacy of acupressure (ACP) in alleviating FMS symptoms, its underlying mechanisms remain poorly understood. This study investigates how ACP modulates central sensitization and inflammatory pathways in a rat model of FM.METHODS: An FM rat model was developed to evaluate the efficacy of ACP therapy. Pain sensitivity and emotional distress were assessed using behavioral tests. Molecular analyses, including Western blot and immunofluorescence, were used to measure MAPK pathway activity (phosphorylation of p38 MAPK and JNK MAPK), glial cell activation (microglia and astrocytes), and inflammatory cytokine levels (TNF-ɑ, IL-6). Post-translational modifications were analyzed to explore anti-inflammatory mechanisms.RESULTS: ACP therapy significantly reduced pain sensitivity in FM rats. Mechanistically, ACP inhibited phosphorylation of p38 MAPK and JNK MAPK, suppressed glial cell activation, reduced pro-inflammatory cytokine release, and eventually attenuated central sensitization. The anti-inflammatory effects were mediated primarily by regulating post-translational modifications rather than altering protein synthesis or degradation. Additionally, ACP restored muscle function and demonstrated therapeutic effects on somatic manifestations of FMS.CONCLUSION: ACP exerts multimodal therapeutic effects on FMS through dual modulation of MAPK signaling, which targets central sensitization and inflammation through precision-driven post-translational regulation. Its ability to alleviate physical symptoms highlights its potential as a targeted intervention for FMS. These findings provide mechanistic insights into ACP's clinical efficacy and support its integration into FMS management strategies.PMID:40629417 | DOI:10.1186/s13018-025-05986-8