Functional connectivity of the periaqueductal grey subdivisions is disrupted in chronic low back pain

Chronic low back pain (cLBP) is a common musculoskeletal condition worldwide. Previous studies have implicated the periaqueductal grey (PAG) in pain modulation of cLBP. However, the PAG has subdivisions with distinct functions. Characterizing the function of PAG subdivisions will help to elucidate the specific role of PAG in cLBP. Here, we explored the functional connectivity alterations of the PAG subdivisions in 75 cLBP patients as compared with 75 healthy controls, and correlated the neuroimaging findings with clinical measures. Results suggested significantly enhanced resting-state functional connectivity (rsFC) in the bilateral ventrolateral PAG (bivlPAG)-bilateral postcentral gyrus (PoCG)/left superior parietal lobe (SPL, p = 0.037, false discovery rate [FDR] corrected) and decreased rsFC in the bilateral lateral PAG-bilateral precuneus/posterior cingulate cortex (PCC, p < 0.001, FDR corrected) pathways in cLBP subjects compared with healthy controls. When performing attention-demanding task, cLBP subjects showed significantly decreased connectivity between the bivlPAG and dorsal medial prefrontal cortex (dmPFC) (p < 0.001, FDR corrected)/right cerebellum (p = 0.004, FDR corrected), as well as increased connectivity between the bivlPAG and left precentral gyrus (PreCG)/PoCG (p = 0.002, FDR corrected), compared with healthy controls. Negative correlations were suggested between bivlPAG-PoCG/SPL rsFC and depression scores (r = -0.322, p = 0.025, FDR corrected) and between the task-related functional connectivity of the vlPAG-PoCG and disease duration (r = -0.278, p = 0.04, FDR corrected) in the cLBP group. These findings suggest disrupted descending pain modulation via the PAG-S1 pathway and impaired attention modulation via the vlPAG-dmPFC and vlPAG-PreCG/PoCG pathways in cLBP patients.