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This research investigates how acupuncture modifies functional brain networks related to neck pain and its underlying gene expression mechanisms.

May 2, 2026Open Access

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

Key Points

This research investigates how acupuncture modifies functional brain networks related to neck pain and its underlying gene expression mechanisms.
Cross-scale multi-omics analysis of 100 neck pain patients randomized to verum or sham acupuncture groups.
Participants received treatment twice a week for 2 weeks, followed by assessments using Visual Analog Scale (VAS) and neuroimaging techniques.
Data analyzed using Partial Least Squares (PLS) regression and integrated with transcriptome data from Allen Human Brain Atlas.
Both acupuncture groups showed significant pain reduction as measured by post-treatment VAS (p < 0.001), with the verum group showing greater efficacy (Z = −6.877, p < 0.001).
Verum acupuncture notably reduced functional connectivity between the right thalamus and left anterior cingulate cortex (T = −4.498) and the right Rolandic operculum (T = −4.532, voxel-level p < 0.01).
Gene-FC analysis explained 39.83% of variance in functional connectivity with significant correlations to genes involved in immune response and synaptic pathways (r = 0.445, p = 0.0011).

Abstract

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.

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