Altered Resting-State Connectivity with Pain-Related Expectation Regions in Female Patients with Severe Knee Osteoarthritis

PURPOSE: Expectation affects pain experience in humans. Numerous studies have reported that pre-stimulus activity in the anterior insular cortex (aIC), together with prefrontal and limbic regions, integrated pain intensity and expectations. However, it is unclear whether the resting-state functional connectivity (rs-FC) between the aIC and other brain regions affects chronic pain. The purpose of this study was to examine the rs-FC between the aIC and the whole brain regions in female patients with severe knee osteoarthritis (OA). PATIENTS AND METHODS: Nineteen female patients with chronic severe knee OA and 15 matched controls underwent resting-state functional magnetic resonance imaging. We compared the rs-FC from the aIC seed region between the two groups. A disease-specific measurement of knee OA was performed. RESULTS: The aIC showed stronger rs-FC with the right orbitofrontal cortex (OFC), subcallosal area, and bilateral frontal pole compared with controls. The strength of rs-FC between the left aIC and the right OFC was positively correlated with the knee OA pain score (r = 0.49, p = 0.03). The strength of rs-FC between the right aIC and right OFC was positively correlated with the knee OA total score (r = 0.48, p = 0.036) and pain score (r = 0.46, p = 0.049). The OFC, subcallosal area, and frontal pole, together with the aIC, were activated during anticipation of pain stimulus. These areas have been reported as representative pain-related expectation regions. CONCLUSION: This was the first study to show the stronger rs-FCs between the aIC and other pain-related expectation regions in female patients with severe knee OA. Female sex and preoperative pain intensity are risk factors of persistent postoperative pain after total knee arthroplasty. It is suggested that the functional relationship between pain-related expectation regions affects the formation of severe knee OA and persistent postoperative pain following total knee arthroplasty.