Primary dysmenorrhea (PDM, menstrual pain without pelvic abnormality) is the most common gynecological disorder for women in the reproductive age. It is characterized by cramping pain and enhanced pain sensitivity during the menstruation period. PDM has been associated with peripheral and central sensitization. Abnormal brain mechanisms may further contribute to development and maintenance of the state. Using fluoro-deoxyglucose positron emission tomography, increased activity was observed in prefrontal/orbitofrontal regions and left ventral posterior thalamus while decreased activity mainly was observed in sensorimotor regions of the left hemisphere at onset compared to offset of PDM. These results were specific to menstrual pain and were not found in menstrual matched controls. Orbitofrontal activities were positively related to while somatosensory activities where negatively related to subjective pain ratings. These results show that ongoing menstrual pain in PDM is accompanied by abnormal brain metabolism. Disinhibition of thalamo-orbitofrontal-prefrontal networks may contribute to the generation of pain and hyperalgesia in PDM possibly by maintaining spinal and thalamic sensitization while increasing negative affect. Excessive excitatory input during menstrual pain may induce compensatory inhibitory mechanism in several somatic sensorimotor regions.