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Chronic neck and shoulder pain with cervical spondylotic radiculopathy (CNSP-CSR) is one of the most common clinical chronic pain diseases. This study aimed to investigate the abnormal patterns in functional connectivity (FC) pertaining to the periaqueductal gray matter (PAG) in patients with CNSP-CSR. A seed-based FC analysis was carried out for the right ventrolateral PAG and a correlation analysis was carried out with pain intensity, duration, and the extracted mean z scores. The PAG FC was significantly positively associated with the right orbital inferior frontal gyrus, supramarginal gyrus/postcentral gyrus, putamen, and the left anterior cingulate cortex, and significant negative FC was observed in the right lingual gyrus/occipital cortex in patients with CNSP-CSR. A significant negative correlation was found between the pain intensity and the mean z scores in the left anterior cingulate cortex. Our study provides evidence to show that patients with CNSP-CSR have abnormal FC in the PAG-centered pain modulation network. Knowledge of this abnormal FC might lead to a better understanding of the mechanism underlying CNSP-CSR, especially the descending pain modulation system involved in chronic pain.