Influence of estrogen on brain activation during stimulation with painful heat

Several studies have shown that women express higher pain sensitivity during periods of low estrogen than during periods of high estrogen. The aim of this study was to show whether the difference in pain sensitivity could be visualized as a function of brain activity by means of functional magnetic resonance imaging (fMRI).

Nine healthy, pain-free women (mean age, 26.2 +/- 6.9 years) with a natural, regular menstrual cycle participated in the study. Whole-brain fMRI data were acquired during a period of high and during a period of low estrogen at 1.5 T using echo-planar imaging with near-isotropic spatial resolution and a temporal resolution of 4 seconds. Heat pain thresholds were obtained before the scans, and pain ratings were obtained before and after each scan. Blood samples were taken after each scan to verify the appropriate level of estrogen.

The heat pain thresholds during the low (46.4 degrees +/- 3.5 degrees C) and high (46.4 degrees +/- 3.8 degrees C) estrogen conditions were not significantly different. The pain ratings before (4.6 +/- 2.2 low versus 3.6 +/- 2.1 high) and during the scans (4.4 +/- 2.4 low versus 4.7 +/- 2.3 high) also did not differ between the 2 conditions. Generally, similar patterns of activation were observed for both estrogen conditions. However, significant differences were found in the magnitude of activation of the anterior part of the anterior cingulate (BA 24/32), the cerebellum, and the precuneus. Furthermore, activations in the anterior part of the anterior cingulate, left cerebellum, and precuneus were unique to the low-estrogen phase. These regions have been linked with attention to or anticipation of pain.

The results of this study suggest that the affective component of pain may be enhanced during the low-estrogen phase of the menstrual cycle in healthy women.