Spinal Manipulation Therapy Remodels CA1-Centered Default Mode Network to Alleviate Comorbid Low Back Pain and Depression-Like Behaviors in Rats.

Abstract

Objective: 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).

Methods: 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.

Results: 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.

Conclusion: 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.