Brain Microstructural and Functional Connectivity Changes After Chinese Manual Therapy in Chronic Neck Pain: A Multimodal MRI Study.

Chronic neck pain (CNP) is characterized by persistent pain and disability, often accompanied by alterations in brain structure and function. Although Chinese manual therapy has demonstrated clinical efficacy in relieving CNP, its central neural mechanisms remain poorly understood. Thirty patients with CNP and 32 age- and sex-matched healthy controls (HCs) underwent 5.0-T magnetic resonance imaging (MRI) including neurite orientation dispersion and density imaging (NODDI) and resting-state functional MRI(rs-fMRI). Patients received 12 sessions of Chinese manual therapy administered three times per week over a 4-week period. Clinical outcomes were evaluated with the Visual Analog Scale (VAS), Neck Disability Index (NDI_score), and Pain Catastrophizing Scale (PCS). Between-group and within-group differences were analyzed using appropriate parametric or nonparametric tests with false discovery rate correction. Chinese manual therapy significantly reduced VAS (mean ± SD, -3.18 ± 1.35; p < 0.001), NDI (-7.97 ± 6.20; p < 0.001), and PCS (-4.17 ± 7.80; p =.006) scores, indicating substantial pain relief and functional recovery. At baseline, patients exhibited decreased neurite density index (NDI) and increased orientation dispersion index (ODI) in the right thalamus, left posterior cingulate cortex, and left precuneus (all p < 0.01), along with altered functional connectivity (FC) within thalamocortical and default-mode networks. After treatment, NDI increased and ODI decreased toward HC levels, while thalamus-anterior cingulate hyperconnectivity decreased (ΔFC = -0.10 ± 0.05; p < 0.01) and thalamus-medial superior frontal connectivity increased (ΔFC = 0.09 ± 0.04; p <0.05). Reductions in thalamocortical FC were significantly associated with pain improvement (ΔVAS vs ΔFC, r = 0.73; p <0.05). No adverse events occurred. Chinese manual therapy was associated with significant pain and disability reduction in CNP, accompanied by concurrent microstructural and functional reorganization within thalamic and default-mode network regions. These findings provide neuroimaging evidence supporting a central neural correlate of Chinese manual therapy that extends beyond purely peripheral biomechanical explanations.