Randomized trial assesses massage impact on brain activity and pain in nerve injury model, indicating therapeutic potential.
BACKGROUND: Neuropathic pain (NP) is associated with maladaptive functional reorganization of the brain, yet the central mechanisms through which massage therapy exerts its analgesic effects remain poorly understood. This study aimed to investigate the impact of acupoint massage on spontaneous neural activity in a rat model of chronic constriction injury (CCI) of the sciatic nerve using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Male Sprague-Dawley rats (N = 45) were randomly allocated into three groups: control, CCI model, and CCI with massage intervention. The massage group received daily acupoint pressing therapy from postoperative day 4 to day 17. Mechanical paw withdrawal threshold (PWT) and thermal paw withdrawal latency (PWL) were assessed at baseline and on days 4, 7, 10, and 17 post-modeling. rs-fMRI scans were acquired at three time points (pre-modeling, day 7, and day 17) using a 9.4T small-animal MRI system. Whole-brain amplitude of low-frequency fluctuations (ALFF) was analyzed to evaluate spontaneous neural activity. RESULTS: CCI modeling induced significant alterations in ALFF across multiple brain regions involved in sensory, affective, and cognitive processing, including the amygdala, hippocampus, insular cortex, and somatosensory cortex. Massage intervention produced a significant group × time interaction effect in the left hippocampus (voxel p < 0.005, cluster p < 0.05 FWE corrected). Specifically, at 7 days post-modeling, ALFF values in the massage group were significantly lower than those in the model group (p = 0.0357), indicating early attenuation of CCI-induced hippocampal hyperactivity. Behaviorally, massage intervention significantly elevated PWT and PWL from day 7 onward (p < 0.001), with sustained improvement through day 17. CONCLUSIONS: Massage therapy alleviates NP through modulation of spontaneous neural activity across multiple brain regions, with dynamic regulation of hippocampal plasticity emerging as a critical central mechanism. The early normalization of hippocampal hyperactivity may serve as a potential neuroimaging biomarker for massage-mediated analgesia and provides experimental evidence supporting the clinical application of massage for NP management.
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