Spinal Manipulation Therapy Remodels CA1-Centered Default Mode Network to Alleviate Comorbid Low Back Pain and...

To explore neuroimaging biomarkers associated with alleviation of both pain and negative emotions among rats with low back pain (LBP) that received spinal manipulation therapy (SMT).

Forty Sprague-Dawley rats were randomly allocated to the control, model, SMT, and sham-SMT groups, with 10 rats in each group. A LBP rat model was established by chronically compression of dorsal root ganglion. The rats underwent 7.0 T magnetic resonance imaging (MRI) scans before and after SMT. Pain and negative emotions were also measured. Structural and functional MRI data were analyzed using network-based statistic (NBS) correction to identify regions of interest (ROIs) with significant differences in connectivity, and the Pearson's correlations between these ROIs and behavioral data were examined.

After SMT, pain and depression-like behaviors were alleviated in LBP rats, accompanied by concordant alterations in regional spontaneous brain activity. Subsequent zFC analysis with NBS correction revealed significant connectivity alterations involving left cornu ammonis 1 (CA1_L), right cornu ammonis 1 (CA1_R), right lateral entorhinal cortex (LEC_R), and left primary visual cortex, binocular area (V1B_L). Positive correlations were observed between CA1_R-related connectivity and paw withdrawal latency (r=0.409, P=0.024) and between CA1_L-related connectivity and paw withdrawal threshold (r=0.371, P=0.029). In contrast, the depression index was negatively correlated with connectivity involving V1B_L, CA1_R, LEC_R, and CA1_L (r=-0.326, -0.314, -0.336, and -0.347, respectively, all P<0.05). No significant correlations with anxiety-related measures were identified.

The neurofunctional remodeling of the default mode network, which is centered around the CA1 region, is likely a key neuroimaging biomarker for regulating comorbid pain and depression-like behaviors in LBP rats after SMT.