Electrostimulation of the trigeminal ganglion (TGES) has shown good results in treatment of trigeminopathic pain in selected patients. To map the mechanisms of TGES analgesia, we determined changes in relative regional cerebral blood flow (rCBF) in ten patients with trigeminopathic pain using positron emission tomography. The patients were scanned before stimulation (habitual pain), after short-term stimulation (1 min, stTGES) and after long-term stimulation (ltTGES). Highly significant pain alleviation was reported after ltTGES. Relative rCBF changes after stTGES, which was without significant pain relief, were attributed mainly to intrinsic TGES effects. A statistical comparison of the subtraction images of ltTGES and stTGES disclosed significant rCBF increases after ltTGES in rostral parts of anterior cingulate cortex (ACC) and neighboring orbitofrontal and medial frontal cortices. Regression analysis of rCBF changes and subjective ratings of pain revealed an inverse relationship in the ipsilateral rostral ACC, and only rCBF changes in the caudal part of the contralateral ACC were consistent with the encoding of pain. The present study provides evidence for a pain modulating role of the rostral ACC, critically important in electrostimulation-induced analgesia, and identifies the caudal ACC as a region encoding pain sensation.