Functional and structural brain alterations associated with menstrual pain

Dysmenorrhea is a widely presented gynecological disorder for women in the childbearing age. Females with dysmenorrhea suffer from disabling, cramping pain emanating from the lower abdomen with the onset of menstrual flow and the pain persists for 24-72 hours. Recent studies further disclosed that central sensitization exists in dysmenorrhea as hyperalgesia spans different spinal segments and multiple tissue systems (e.g., skin and muscle) and extends to non-referred pain areas during the menstrual phase. Moreover, menstrual pain is associated with functional and structural alterations in highly specified regions involved in pain transmission and modulation, generation of the affective experience, and regulation of endocrine function. The adaptive and mal-adaptive changes in the brain may be engaged simultaneously and dynamically and that some of these regions may underpin the hyperalgesia in dysmenorrhea. The functional and structural brain alterations may either be either state-related or trait-related. Where state-related changes are associated with the presence of menstrual pain, trait-related changes exist even in the absence of symptoms. When comparing pain and pain-free states, the rapid state-related structural changes in several regions correlating with the severity of the menstrual pain experience, suggesting that these changes are primary changes rather than epiphenomena. Some of the observed state-related structural alterations even persisted into the pain-free state indicating an accumulating effect of the cyclic menstrual pain. This notion is supported by a correlation of gray matter volume in these regions with menstrual pain duration. More specifically, regions involved in pain modulation and affect regulation exhibited hypertrophy and regions associated with pain transmission showed atrophic changes. Using positron emission topography to study state-related changes in glucose metabolism, the alterations in central processing of menstrual pain suggest that a disinhibitiondisinhibition of a thalamo-orbitofrontal-prefrontal network may promote central sensitization during menstruation. On the other hand, reduced metabolism was also found in sensory-discriminative areas, indicating a down regulation in pain transmission pathways. These findings are congruent with the structural brain alterations observed in dysmenorrhea. Overall, these results indicate that the adolescent brain is vulnerable to menstrual pain. Considering the high prevalence rate of dysmenorrhea and the early onset of primary dysmenorrhea, these findings mandate a great demand to revisit dysmenorrhea regarding its impact on the brain and other clinical pain conditions. Like the migraine, dysmenorrhea might be considered a chronic disease with episodic features but largely confined to the menstrual phase.