Recent functional brain imaging studies with positron emission tomography (PET), in painful peripheral mononeuropathy and nitroglycerin-provoked cluster headache attacks, suggest a preference of the right hemisphere, especially the anterior cingulate cortex (ACC) and the medial prefrontal cortex (MPFC), in attributing emotional valence and attention to the pain suffering. We have investigated the central processing of painful trigeminal neuropathy (PTN) in patients treated with electric extradural precentral gyrus stimulation (PCGS). Increased regional cerebral blood flow (rCBF) was detected in the right caudal ACC [Brodmann area (BA) 24] and anterior limbic thalamus, while a decreased activity was observed in the right MPFC (BA 9/32) during the habitual-pain state, in comparison with the pain-alleviated state regardless of the inflicted side of PTN. The involvement of BA 9/32 and the anterior limbic thalamus spatially extended to the left hemisphere, but the local maxima and a significant negative correlation between the rCBF changes in the two structures were found only in the right hemisphere. The activation of the caudal BA24 further supports the theory that ACC is crucial for the suffering in chronic pain. Our study not only verifies the preferential role of the right hemisphere in the appreciation of pain suffering, but further supports that sustained chronic pain, being devoid of the motivational component of an escape response, targets the right hemisphere, particularly the BA24 of the ACC. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.