Functional connectivity changes in the thalamocortical network due to neck pain and the multiscale regulatory effects of acupuncture: a cross-scale multi-omics neuroimaging study

BACKGROUND: Neck pain correlates with multiscale brain abnormalities, but cross‐scale mechanisms of acupuncture analgesia are unclear. This study aimed to: (1) Explore differential modulation of thalamic functional networks by verum vs. sham acupuncture; (2) Examine associations between functional connectivity changes and micro gene expression to unravel its multiscale mechanisms. METHODS: A total of 130 participants were initially enrolled, and 100 eligible neck pain patients were randomized 1:1 to the verum (n = 50) or sham (n = 50) acupuncture groups. Finally, 49 patients in each group were included for the final analysis due to one case of exclusion in each group, with treatment administered twice a week for 2 weeks. Visual Analog Scale (VAS), resting‐state functional magnetic resonance imaging (fMRI), and Allen Human Brain Atlas (AHBA) transcriptome data were analyzed via Partial Least Squares (PLS) regression. RESULTS: Both groups showed reduced post‐treatment VAS (p < 0.001), with the verum group exhibiting a superior effect (Z = ‐6.877, p < 0.001). Neuroimaging revealed that verum acupuncture (VA) specifically induced significant decreases in functional connectivity (FC) between the right thalamus and left anterior cingulate cortex (T = ‐4.498) as well as between the right thalamus and right Rolandic operculum (T = ‐4.532, voxel‐level p < 0.01, cluster‐level p < 0.05), an effect absent in the sham acupuncture group (SA). Gene‐ FC association analysis indicated that PLS2 component explained 39.83% of FC variance (P spin: permutation test p < 0.05), with weight genes showing significant spatial correlation to connectivity changes (r = 0.445, P spin = 0.0011). A total of 809 genes were enriched in the innate immune response and phosphorylation regulation pathways, whereas 1,222 genes were enriched in the GABA‐ergic synapse and synaptic membrane‐related pathways. CONCLUSION: VA relieves pain via modulating thalamus‐anterior cingulate cortex networks, involving immune‐inflammation and neural inhibition, providing first multi‐scale validation integrating neuroimaging and transcriptomics. CLINICAL TRIAL REGISTRATION: This trial was registered with the International Traditional Medicine Clinical Trial Registry (registration number: ITMCTR2023000001) prior to participant enrollment.