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Objective. Cognitive behavioral therapies decrease pain and improve mood and function in people with osteoarthritis. This study assessed the effects of coping strategies on the central processing of knee pain in people with osteoarthritis of the knees. Methods. Mechanical pressure was applied to exacerbate knee pain in 28 people with osteoarthritis of the knee. Reports of pain intensity and functional magnetic resonance imaging measures of pain related brain activity were recorded with and without the concurrent use of pain coping skills. Results. Coping skills led to a significant reduction in pain report (Coping 5 2.6460.17, Not Coping 53.2860.15, P< 0.001). These strategies were associated with increased activation in pain modulatory regions of the brain (medial prefrontal and rostral anterior cingulate cortices, Pcorrected < 0.05) and decreased pain-related activation in regions that process noxious input (midcingulate cortex,supplementary motor area, secondary somatosensory cortex, and anterior parietal lobule, Pcorrected < 0.05). The magnitude of the decrease in pain report during the use of pain coping strategies was found to be proportional to the decrease in pain-related activation in brain regions that code the aversive/emotional dimension of pain (anteriorinsula, inferior frontal gyrus, orbitofrontal cortex, Pcorrected < 0.05) but did not differ between groups with and without training in coping skills. However,training in coping skills reduced the extent towhich brain responses to noxious input were influencedby anxiety. Conclusions. The results of this study support previous reports of pain modulation by cognitive pain coping strategies and contribute to the current understanding of how analgesia associated with the use of pain coping strategies is represented in the brain. Refereed/Peer-reviewed