ObjectiveChronic pain, a major global public health burden, is primarily driven by altered central pain processing, which conventional treatments rarely target directly. This systematic review and meta-analysis synthesized RCT evidence to quantify acupuncture’s modulatory effects on brain networks associated with altered central pain processing, validate its clinical efficacy/safety, and explore brain network-clinical outcome associations.MethodsComprehensive searches of English/Chinese databases (2016–2025) identified RCTs of acupuncture for chronic pain with neuroimaging. Two researchers independently performed study selection, data extraction, and bias assessment. Meta-analysis used RevMan 5.4; heterogeneity was evaluated via I2/Q test, with correlation analysis and GRADE evidence quality assessment.ResultsSeventeen high-quality RCTs comprising 750 patients, with osteoarticular pain and migraine as main subtypes, were included. Acupuncture significantly improved neuroimaging indicators in the anterior cingulate cortex (ACC) and insula (MD = 0.27, p < 0.00001), primary somatosensory cortex (S1) and thalamus (MD = 0.30, p < 0.00001), and default mode network (DMN) (MD = 0.29, p < 0.00001). Clinically, acupuncture reduced Visual Analogue Scale (VAS) scores (MD = -2.31, p < 0.00001) and increased pain relief rate (OR = 4.30, p < 0.00001), with only mild adverse events reported. Osteoarticular pain demonstrated more pronounced efficacy. No significant publication bias was detected. The GRADE assessment rated the evidence for pain relief rate as high.ConclusionAcupuncture exerts dual effects by alleviating clinical pain - exceeding the minimal clinically important difference (MCID) for VAS - and modulating brain networks implicated in altered central pain processing. It is a safe and valuable non-pharmacological intervention, with standardized protocols and subtype-specific application recommended. However, the evidence is constrained by a limited number of studies, heterogeneity in pain subtypes and neuroimaging modalities, and short follow-up durations. Larger RCTs and multimodal neuroimaging studies are needed for further validation.Systematic review registrationRegistered in PROSPERO (CRD420261290299); URL: https://www.crd.york.ac.uk/prospero/.
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