title: The role of circulating sex hormones in menstrual cycle-dependent modulation of pain-related brain activation.
abstract: Sex differences in pain sensitivity have been consistently found, but the basis for these differences is incompletely understood. The present study assessed how pain-related neural processing varies across the menstrual cycle in normally cycling, healthy women, and whether menstrual cycle effects are based on fluctuating sex hormone levels. Fifteen subjects participated in 4 test sessions during their menstrual, midfollicular, ovulatory, and midluteal phases. Brain activity was measured while nonpainful and painful stimuli were applied with a pressure algometer. Serum hormone levels confirmed that scans were performed at appropriate cycle phases in 14 subjects. No significant cycle phase differences were found for pain intensity or unpleasantness ratings of stimuli applied during functional magnetic resonance imaging scans. However, lower pressure pain thresholds were found for follicular compared with other phases. Pain-specific brain activation was found in several regions traditionally associated with pain processing, including the medial thalamus, anterior and middle insula, midcingulate, primary and secondary somatosensory cortices, cerebellum, and frontal regions. The inferior parietal lobule, occipital gyrus, cerebellum, and several frontal regions showed interaction effects between stimulus level and cycle phase, indicating differential processing of pain-related responses across menstrual cycle phases. Correlational analyses indicated that cycle-related changes in pain sensitivity measures and brain activation were only partly explained by varying sex hormone levels. These results show that pain-related cerebral activation varies significantly across the menstrual cycle, even when perceived pain intensity and unpleasantness remain constant. The involved brain regions suggest that cognitive pain or more general bodily awareness systems are most susceptible to menstrual cycle effects.
authors.affiliation: Department of Neural and Pain Sciences, UMB Research Center for Neuroendocrine Influences on Pain, University of Maryland, Baltimore, MD, USA Pain Clinic, Division of Anesthesiology, Intensive Care and Emergency Medicine, Rudolf Magus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands Department of Diagnostic Radiology, University of Maryland, Baltimore, MD, USA.
authors.forename: Dieuwke S
authors.initials: DS
authors.lastname: Veldhuijzen
authors.forename: Michael L
authors.initials: ML
authors.lastname: Keaser
authors.forename: Deborah S
authors.initials: DS
authors.lastname: Traub
authors.forename: Jiachen
authors.initials: J
authors.lastname: Zhuo
authors.forename: Rao P
authors.initials: RP
authors.lastname: Gullapalli
authors.forename: Joel D
authors.initials: JD
authors.lastname: Greenspan
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001921:Brain / Q000098:blood supply / Q000503:physiopathology*; D001931:Brain Mapping; D005260:Female; D007839:Functional Laterality; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008597:Menstrual Cycle / Q000502:physiology*; D010100:Oxygen / Q000097:blood; D010146:Pain / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D010147:Pain Measurement; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D012739:Gonadal Steroid Hormones; D010100:Oxygen