TY - JOUR
T1 - The role of circulating sex hormones in menstrual cycle-dependent modulation of pain-related brain activation
AU - Veldhuijzen, Dieuwke S.
AU - Keaser, Michael L.
AU - Traub, Deborah S.
AU - Zhuo, Jiachen
AU - Gullapalli, Rao P.
AU - Greenspan, Joel D.
N1 - Funding Information:
This work was supported by P50-AR49555 (J.D.G.) and the University of Maryland General Clinical Research Center grant M01-RR16500. The authors declare no conflicts of interest.
PY - 2013/4
Y1 - 2013/4
N2 - 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.
AB - 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.
KW - Circulating hormones
KW - Functional brain imaging
KW - Menstrual cycle
KW - Pain sensitivity
KW - Pain-related brain activation
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U2 - 10.1016/j.pain.2012.12.019
DO - 10.1016/j.pain.2012.12.019
M3 - Article
C2 - 23528204
AN - SCOPUS:84875472413
SN - 0304-3959
VL - 154
SP - 548
EP - 559
JO - Pain
JF - Pain
IS - 4
ER -